☆ 4.6 Review

White matter injury, cholesterol dysmetabolism, and APP/Abeta dysmetabolism interact to produce Alzheimer's disease (AD) neuropathology: A hypothesis and review

FRONTIERS IN AGING NEUROSCIENCE (2023)

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Article Biochemistry & Molecular Biology

Apolipoprotein E ε4 disrupts oligodendrocyte differentiation by interfering with astrocyte-derived lipid transport

Kingston King-Shi Mok et al.

Summary: Carriers of the APOE4 variant are more susceptible to Alzheimer's disease due to altered lipid and cholesterol transport capabilities. This study examines the impact of APOE4 on oligodendrocytes and finds a disruption in myelination, possibly contributing to the development of Alzheimer's disease.

JOURNAL OF NEUROCHEMISTRY (2023)

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Article Geriatrics & Gerontology

Aging compromises oligodendrocyte precursor cell maturation and efficient remyelination in the monkey brain

Christina Dimovasili et al.

Summary: Age-associated cognitive decline is common among healthy elderly individuals. This study found that white matter loss and myelin damage are strongly associated with this decline. The regenerative capacity of oligodendrocyte precursor cells (OPCs) is reduced in aging, leading to impaired myelin production and remyelination. These findings highlight the importance of maintaining optimal myelin regeneration for preserving cognitive function in aging.

GEROSCIENCE (2023)

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Article Biochemistry & Molecular Biology

Reduced Levels of ABCA1 Transporter Are Responsible for the Cholesterol Efflux Impairment in β-Amyloid-Induced Reactive Astrocytes: Potential Rescue from Biomimetic HDLs

Giulia Sierri et al.

Summary: Astrocytes in the brain are responsible for cholesterol synthesis, but in Alzheimer's disease, astrocytosis occurs, affecting cholesterol metabolism. Aβ-induced astrocytosis impairs cholesterol efflux, possibly due to reduced levels of ABCA1 transporters. Biomimetic HDLs have been designed to promote cholesterol efflux from astrocytes and show potential as a supportive treatment for AD.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Neurosciences

Anti-LINGO-1 antibody treatment alleviates cognitive deficits and promotes maturation of oligodendrocytes in the hippocampus of APP/PS1 mice

Hao Yang et al.

Summary: This study aims to assess the effect of anti-LINGO-1 antibody treatment on cognition and hippocampal oligodendrocytes in an AD transgenic animal model. The results showed that anti-LINGO-1 antibody alleviated spatial learning and memory deficits, decreased A beta deposition, and promoted oligodendrocyte differentiation and maturation in the hippocampus.

JOURNAL OF COMPARATIVE NEUROLOGY (2022)

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Article Biochemistry & Molecular Biology

Icariin Ameliorates Alzheimer's Disease Pathology by Alleviating Myelin Injury in 3 x Tg-AD Mice

Hongxia Yu et al.

Summary: Alzheimer's disease (AD) is a neurodegenerative disease characterized by the deposition of beta amyloid, hyperphosphorylation of tau protein, and cell death. This study investigates the potential of icariin (ICA), a prenylated flavonol glycoside, in improving cognitive function in AD model mice. The results show that ICA treatment improves learning and memory, reduces A beta deposition and tau protein phosphorylation in the hippocampus, and increases myelin-related gene expression, suggesting its potential therapeutic effects on AD.

NEUROCHEMICAL RESEARCH (2022)

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Review Neurosciences

Local cholesterol metabolism orchestrates remyelination

Stefan A. Berghoff et al.

Summary: Cholesterol plays a vital role in cell membranes, especially in myelin membranes. Multiple sclerosis is a chronic neurological disorder characterized by immune attacks on myelin. During demyelination, cholesterol is released from damaged myelin, hindering tissue regeneration. Understanding the interplay between cell type-specific cholesterol metabolism, inflammation, and blood-brain barrier integrity can help unravel disease processes and facilitate the development of strategies to promote remyelination.

TRENDS IN NEUROSCIENCES (2022)

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Article Clinical Neurology

Greater Diffusion Restriction in White Matter in Preclinical Alzheimer Disease

Andreana Benitez et al.

Summary: This study aimed to detect and describe amyloid-related white matter changes in preclinical Alzheimer's disease using diffusional kurtosis imaging (DKI) and biophysical modeling. The results showed greater diffusion restriction in white matter, particularly in the extra-axonal space within late myelinating tracts, in Alzheimer's disease patients. The diffusion metrics were able to predict amyloid status incrementally and were associated with other biomarkers.

ANNALS OF NEUROLOGY (2022)

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Article Anatomy & Morphology

Aging and white matter microstructure and macrostructure: a longitudinal multi-site diffusion MRI study of 1218 participants

Kurt G. Schilling et al.

Summary: This study examines the microstructural and macrostructural features of white matter in the aging brain using diffusion magnetic resonance imaging. The findings show that microstructure and macrostructure features are both affected by age, but macrostructure features demonstrate more heterogeneity across different pathways. This suggests that macrostructural features may be more sensitive indicators of white matter decline and can be used in studying aging and various diseases or conditions.

BRAIN STRUCTURE & FUNCTION (2022)

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Article Biochemistry & Molecular Biology

Free Cholesterol Accelerates Aβ Self-Assembly on Membranes at Physiological Concentration

Mohtadin Hashemi et al.

Summary: The effects of membranes on the early-stage aggregation of amyloid beta (A beta) have been studied, showing that direct A beta-membrane interactions dramatically enhance the aggregation process. Cholesterol in membranes significantly enhances the aggregation kinetics and accelerates the formation and dissociation of aggregates. Cholesterol binds A beta monomers and changes their conformation.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Neurosciences

TREM2 in the pathogenesis of AD: a lipid metabolism regulator and potential metabolic therapeutic target

Rui-Yang Li et al.

Summary: TREM2 is an important immune receptor that can impact lipid metabolism in both the central nervous system and the periphery, and may have implications for the pathogenesis of AD. Through pathways including inflammation, insulin resistance, and AD pathology, the association between TREM2 and AD may be mediated by altered lipid metabolism.

MOLECULAR NEURODEGENERATION (2022)

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Article Clinical Neurology

Long-term low-dose acetylsalicylic use shows protective potential for the development of both vascular dementia and Alzheimer's disease in patients with coronary heart disease but not in other individuals from the general population: results from two large cohort studies

Thi Ngoc Mai Nguyen et al.

Summary: This study found a potential inverse association between long-term low-dose ASA use and all-cause dementia, Alzheimer's disease, and vascular dementia, especially in individuals with pre-existing coronary heart disease. Long-term use of low-dose ASA for 10 years or longer showed a strong protective effect, particularly against vascular dementia.

ALZHEIMERS RESEARCH & THERAPY (2022)

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Article Geriatrics & Gerontology

Diabetes Mellitus-Related Neurobehavioral Deficits in Mice Are Associated With Oligodendrocyte Precursor Cell Dysfunction

Li-Ping Wang et al.

Summary: Recent clinical studies have shown an increased incidence of neurobehavioral disorders in patients with diabetes mellitus. The severity of diabetes is associated with the progression of white matter hyperintensity on brain imaging, which increases the risk of cognitive impairment. This study investigated whether hyperglycemia-induced neurological deficits are related to dysfunction of oligodendrocyte precursor cells.

FRONTIERS IN AGING NEUROSCIENCE (2022)

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Review Neurosciences

Connecting the Dots Between Hypercholesterolemia and Alzheimer's Disease: A Potential Mechanism Based on 27-Hydroxycholesterol

Mingan Wu et al.

Summary: Alzheimer's disease (AD), the most common cause of dementia, is associated with genetic and environmental factors, with hypercholesterolemia being one of the risk factors. Multiple epidemiological studies have reported a positive association between AD and serum cholesterol levels, and experimental studies have shown that elevated cholesterol levels accelerate AD pathology. However, the mechanism by which hypercholesterolemia accelerates AD pathogenesis is unclear. This review focuses on the role of oxysterols in cholesterol metabolism in the brain and aims to uncover the link between hypercholesterolemia and AD. Specifically, 27-hydroxycholesterol (27-OHC), a major peripheral oxysterol that enters the brain, influences beta-amyloid (A beta) production and elimination, as well as other pathogenic mechanisms of AD. While cholesterol-lowering drugs have shown mixed results in improving cognitive function in AD, drugs targeting cholesterol exocytosis and conversion have shown benefits in improving AD pathology. Additionally, herbs and natural compounds with cholesterol-lowering properties may also play a role in improving cognition. In conclusion, hypercholesterolemia is a causative risk factor for AD, and 27-OHC is a potential mechanism through which hypercholesterolemia promotes AD pathology. Drugs regulating cholesterol metabolism could be beneficial for AD, but further research is needed to unravel the mechanisms involved in 27-OHC, leading to new therapeutic strategies for AD.

FRONTIERS IN NEUROSCIENCE (2022)

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Article Neurosciences

Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination

Na Wang et al.

Summary: This study reveals significant differences in the activation and function of microglia depending on apoE isoforms, with apoE2 microglia being more efficient in clearing lipid-rich myelin debris while apoE4 microglia displaying reduced clearance efficiency. Moreover, apoE4 microglia show impaired lipid metabolism, while apoE2 microglia demonstrate superior ability to metabolize myelin-enriched lipids. These findings provide critical mechanistic insights into how apoE isoforms differentially regulate microglial function and the maintenance of myelin dynamics, which may inform novel therapeutic avenues for targeting microglial dysfunctions in neurodegenerative diseases.

MOLECULAR NEURODEGENERATION (2022)

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Article Multidisciplinary Sciences

APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes

Joel W. Blanchard et al.

Summary: APOE4 has widespread effects on gene expression in the human brain, particularly in relation to cholesterol homeostasis and transport. Aberrant cholesterol deposition in oligodendrocytes leads to reduced myelination, while pharmacologically facilitating cholesterol transport improves learning and memory. This study provides insights into the impact of APOE4 on the aging human brain and suggests potential therapeutic strategies for Alzheimer's disease.

NATURE (2022)

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Article Clinical Neurology

Activation of Wnt/β-catenin pathway mitigates blood-brain barrier dysfunction in Alzheimer's disease

Qi Wang et al.

Summary: Alzheimer's disease is a neurodegenerative disorder characterized by neurological and cognitive declines. Dysfunction of the blood-brain barrier is a major contributor to the disease, especially in the early stages. By activating the Wnt/beta-catenin pathway, specifically through LRP6, the blood-brain barrier dysfunction induced by amyloid-beta can be restored, offering a potential treatment strategy for Alzheimer's disease.

BRAIN (2022)

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Article Clinical Neurology

LDL cholesterol is associated with higher AD neuropathology burden independent of APOE

Aliza P. Wingo et al.

Summary: This study found that LDL-C is associated with various neuropathological manifestations of AD independent of APOE, suggesting that LDL-C may be a modifiable risk factor for AD.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2022)

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Article Clinical Neurology

Apolipoprotein E ε4 Mediates Myelin Breakdown by Targeting Oligodendrocytes in Sporadic Alzheimer Disease

Gerald Wai-Yeung Cheng et al.

Summary: White matter degradation in the frontal lobe is an early detectable change in aging and Alzheimer's disease, and the APOE4 gene is strongly associated with this degradation. Research has found that APOE4 directly triggers myelin pathology rich in cholesterol, rather than being an indirect consequence of amyloid plaque formation or neuronal loss.

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY (2022)

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Article Biochemistry & Molecular Biology

High cholesterol and 27-hydroxycholesterol contribute to phosphorylation of tau protein by impairing autophagy causing learning and memory impairment in C57BL/6J mice

Tao Wang et al.

Summary: Cholesterol and its derivative 27-OHC play a role in the pathogenesis of Alzheimer's disease, and phosphorylated tau is involved. Experimental results show that dietary cholesterol impairs learning and memory, and impaired autophagy is related to this effect.

JOURNAL OF NUTRITIONAL BIOCHEMISTRY (2022)

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Article Neurosciences

DHCR24 Knockdown Induces Tau Hyperphosphorylation at Thr181, Ser199, Ser262, and Ser396 Sites via Activation of the Lipid Raft-Dependent Ras/MEK/ERK Signaling Pathway in C8D1A Astrocytes

Meiting Mai et al.

Summary: The deficiency of DHCR24 can lead to hyperphosphorylation of tau protein in astrocytes, which is associated with the lipid raft-dependent signaling pathway. This finding may contribute to the understanding of the pathogenesis of degenerative tauopathies such as Alzheimer's disease.

MOLECULAR NEUROBIOLOGY (2022)

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Article Biochemistry & Molecular Biology

White matter damage as a consequence of vascular dysfunction in a spontaneous mouse model of chronic mild chronic hypoperfusion with eNOS deficiency

Xingyong Chen et al.

Summary: The study suggests that eNOS-deficient mice could serve as an ideal model for studying the earliest events leading to white matter changes in vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD), and for testing potential therapeutic drugs targeting vascular mechanisms contributing to these diseases.

MOLECULAR PSYCHIATRY (2022)

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Article Neurosciences

Peripheral apoE4 enhances Alzheimer's pathology and impairs cognition by compromising cerebrovascular function

Chia-Chen Liu et al.

Summary: Peripheral apoE4 has detrimental effects on cognition and amyloid pathology by compromising vascular integrity and function. It impairs synaptic plasticity and cognition and influences functional pathways such as cell adhesion, lipoprotein metabolism, and complement activation. ApoE3 plasma from young mice improves cognition and reduces vessel-associated gliosis, while liver-expressed apoE4 exacerbates brain amyloid pathology.

NATURE NEUROSCIENCE (2022)

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Article Clinical Neurology

White matter hyperintensities are a prominent feature of autosomal dominant Alzheimer's disease that emerge prior to dementia

Dorothee Schoemaker et al.

Summary: This study found that white matter abnormalities increase in individuals with early-onset autosomal dominant Alzheimer's disease, beginning to increase before clinical symptom onset, which is an independent determinant of cognitive performance.

ALZHEIMERS RESEARCH & THERAPY (2022)

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Review Psychiatry

Effect of Physical Exercise on Cognitive Function of Alzheimer's Disease Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trial

Wei Liu et al.

Summary: This review systematically examines the effects of physical exercise on the cognitive performance of patients with Alzheimer's disease (AD) and its mechanisms. The findings indicate that physical exercise has a positive impact on the cognitive performance of older patients with AD. However, caution should be exercised when interpreting the positive effects of the intervention due to variations in methodological quality, type, frequency, and duration of exercise in the included studies.

FRONTIERS IN PSYCHIATRY (2022)

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Article Biochemistry & Molecular Biology

Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer's Disease

Amandine Jullienne et al.

Summary: This study utilized the 3xTg-AD mouse model to examine the role of vascular dysfunction and structural abnormalities in the progression of Alzheimer's disease. The findings demonstrate progressive alterations in individual cortical vessels and the cortical vascular network, potentially identifying unique diagnostic signatures of AD progression.

BIOMEDICINES (2022)

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Article Multidisciplinary Sciences

Co-expression network analysis of human tau-transgenic mice reveals protein modules associated with tau-induced pathologies

Kazuya Tsumagari et al.

Summary: This study used quantitative proteomics to analyze disease model mice and identified protein co-expression modules associated with tau protein aggregates, which were also preserved in AD brains. The findings provide insights into the molecular basis of tau-induced neurodegeneration, including AD.

ISCIENCE (2022)

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Article Neurosciences

White matter integrity and key structures affected in Alzheimer's disease characterized by diffusion tensor imaging

Danqing Xiao et al.

Summary: White matter degeneration is suggested as an early predictor of Alzheimer's disease, with specific brain regions such as the cingulum gyrus and uncinate fasciculus showing significant changes. Age is a key risk factor for AD, while gender and education do not show significant associations. The study highlights the importance of focusing on specific brain regions for the staging of AD based on DTI measures.

EUROPEAN JOURNAL OF NEUROSCIENCE (2022)

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Review Medicine, Research & Experimental

Alzheimer's disease failed clinical trials

Shreya Asher et al.

Summary: This article reviews the history of clinical trials for Alzheimer's disease and analyzes the reasons for their failures.

LIFE SCIENCES (2022)

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Article Neurosciences

Specific Mutations in the Cholesterol-Binding Site of APP Alter Its Processing and Favor the Production of Shorter, Less Toxic Aβ Peptides

Linda Hanbouch et al.

Summary: Excess brain cholesterol is strongly associated with Alzheimer's disease. This study found that the presence of a cholesterol-binding site in the amyloid precursor protein (APP) regulates its processing. Mutations in this site affected the secretion of amyloid-beta peptides and produced shorter toxic peptides. Cholesterol levels also influenced the production of these peptides, with higher cholesterol resulting in increased production.

MOLECULAR NEUROBIOLOGY (2022)

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Review Neurosciences

Cholesterol as a key player in amyloid β-mediated toxicity in Alzheimer's disease

Vladimir Rudajev et al.

Summary: Alzheimer's disease is a neurodegenerative disorder characterized by the production and aggregation of amyloid beta, which leads to cell membrane disruption and cell death. Cholesterol, as a major component of cell membranes, plays a significant role in the progression of AD, although its effects are inconsistent.

FRONTIERS IN MOLECULAR NEUROSCIENCE (2022)

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Article Cell & Tissue Engineering

Human tau mutations in cerebral organoids induce a progressive dyshomeostasis of cholesterol

Stella M. K. Glasauer et al.

Summary: Mutations in the MAPT gene can cause frontotemporal dementia (FTD), and cholesterol dysregulation may be an early event in neurodegeneration caused by tau mutations.

STEM CELL REPORTS (2022)

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Review Cell Biology

The relationship between amyloid-beta and brain capillary endothelial cells in Alzheimer's disease

Yan-Li Zhang et al.

Summary: Neurovascular dysfunction plays an important role in the onset and progression of Alzheimer's disease, and the blood-brain barrier pathway is a key pathway for amyloid-beta (Aβ) clearance in the brain. Brain capillary endothelial cells are crucial for Aβ clearance mediated by the blood-brain barrier. Dysregulation of Aβ clearance leads to its accumulation in the brain parenchyma. Understanding the interactions between Aβ and brain capillary endothelial cells and developing new therapeutic strategies could improve Aβ clearance in Alzheimer's disease.

NEURAL REGENERATION RESEARCH (2022)

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Article Clinical Neurology

White matter changes from mild cognitive impairment to Alzheimer's disease: a meta-analysis

Linzi Qin et al.

Summary: This meta-analysis identified significantly decreased FA in several brain regions in AD patients compared to those with MCI, suggesting these regions may play a key role in the progression from MCI to AD.

ACTA NEUROLOGICA BELGICA (2021)

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Review Cell Biology

Role of Microglia in Regulating Cholesterol and Tau Pathology in Alzheimer's Disease

Shwetha Nanjundaiah et al.

Summary: Cholesterol, a crucial component of the cell membrane, plays a significant role in the brain by influencing synaptic transmission, neuronal signaling, and neurodegenerative diseases. Dysregulation of cholesterol trafficking is linked to increased production of hyperphosphorylated Tau and Amyloid-beta protein, leading to Alzheimer's disease. Understanding the regulation of cholesterol metabolism and Tau phosphorylation is essential for managing the pathogenesis of Alzheimer's disease.

CELLULAR AND MOLECULAR NEUROBIOLOGY (2021)

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Article Neuroimaging

Plasma lipids are associated with white matter microstructural changes and axonal degeneration

Ane Iriondo et al.

Summary: The study found that dyslipidemia is associated with changes in white matter microstructure and axonal degeneration, potentially serving as a risk factor in the transition from healthy aging to disease.

BRAIN IMAGING AND BEHAVIOR (2021)

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Article Biochemistry & Molecular Biology

Cholesterol in Membranes Facilitates Aggregation of Amyloid β Protein at Physiologically Relevant Concentrations

Siddhartha Banerjee et al.

Summary: The presence of cholesterol in lipid bilayers significantly enhances the aggregation process of Aβ42 at low concentrations, indicating that the lipid composition plays a crucial role in controlling the self-assembly of Aβ oligomers in cellular membranes.

ACS CHEMICAL NEUROSCIENCE (2021)

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Article Biochemistry & Molecular Biology

Chronic Neuroinflammation Induced by Lipopolysaccharide Injection into the Third Ventricle Induces Behavioral Changes

Shufang Na et al.

Summary: Recent studies have shown the existence of Gram-negative bacteria in the brain regardless of immune status, potentially triggering chronic neuroinflammation and leading to Alzheimer's disease. Infectious neuroinflammation may cause depressive-like behaviors and impairment of spatial learning, with cholesterol loss serving as a potential biomarker. The lack of pathological hallmarks of AD in models suggests that Gram-negative bacterial infection may not be the sole cause of AD.

JOURNAL OF MOLECULAR NEUROSCIENCE (2021)

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Article Cell Biology

Cholesterol-lowering drugs reduce APP processing to Aβ by inducing APP dimerization

Vanessa F. Langness et al.

Summary: This study demonstrates that statins can reduce the production of Aβ in human neurons by altering cholesterol metabolism, indicating a potential therapeutic approach for Alzheimer's disease.

MOLECULAR BIOLOGY OF THE CELL (2021)

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Article Neurosciences

The Interplay of ABC Transporters in Aβ Translocation and Cholesterol Metabolism: Implicating Their Roles in Alzheimer's Disease

Tapan Behl et al.

Summary: The review highlights the importance of ABC transporters in Alzheimer's disease (AD) pathogenesis, as they play a crucial role in regulating cholesterol metabolism and Aβ peptide load, while also exerting protective effects against neurotoxic substrates and xenobiotics. Research targeting these proteins may provide a new approach and target for treating AD.

MOLECULAR NEUROBIOLOGY (2021)

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Review Behavioral Sciences

White matter hyperintensities and risks of cognitive impairment and dementia: A systematic review and meta-analysis of 36 prospective studies

He-Ying Hu et al.

Summary: The presence of white matter hyperintensities (WMH) is linked to an increased risk of cognitive impairment and dementia, including Alzheimer's disease and vascular dementia. Higher grade WMH and progressive increases in WMH volume or severity are associated with greater risks of dementia. These findings suggest that WMH could serve as a neuroimaging indicator of dementia.

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS (2021)

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Article Clinical Neurology

Apolipoprotein E homozygous? 4 allele status: Effects on cortical structure and white matter integrity in a young to mid-age sample

Janik Goltermann et al.

Summary: The present study investigated the association between APOE genotype and cortical gray matter structure as well as white matter microstructure. The findings showed pronounced and widespread reductions in cortical surface area and white matter microstructure in homozygous APOE 84 carriers, supporting a global rather than regionally specific effect of the allele status.

EUROPEAN NEUROPSYCHOPHARMACOLOGY (2021)

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Article Chemistry, Physical

Cholesterol Molecules Alter the Energy Landscape of Small Aβ1-42 Oligomers

Son Tung Ngo et al.

Summary: Through molecular dynamics simulations, it was found that interactions with cholesterol molecules completely altered the energy landscape of small A beta 42 oligomers, which cannot be replicated in the brain extracellular space.

JOURNAL OF PHYSICAL CHEMISTRY B (2021)

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Article Biochemistry & Molecular Biology

Influential role of 7-Ketocholesterol in the progression of Alzheimer’s disease

K. Mahalakshmi et al.

PROSTAGLANDINS & OTHER LIPID MEDIATORS (2021)

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Article Neurosciences

White matter aging drives microglial diversity

Shima Safaiyan et al.

Summary: Research has identified white matter-associated microglia (WAMs) as a protective response during aging, characterized by phagocytic activity and lipid metabolism gene activation. WAMs depend on triggering receptor expressed on myeloid cells 2 (TREM2) signaling and are independent of apolipoprotein E (APOE) in contrast to mouse models of Alzheimer's disease.

NEURON (2021)

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Review Neurosciences

ApoE4 activates C/EBPβ/δ-secretase with 27-hydroxycholesterol, driving the pathogenesis of Alzheimer's disease

Zhi-Hao Wang et al.

Summary: The study demonstrates that ApoE4 and 27-OHC can co-activate the C/EBPβ/δ-secretase pathway, mediating Alzheimer's disease pathogenesis through neuronal Aβ and inflammatory cytokines. This effect is dependent on cholesterol metabolism and can be diminished by interventions targeting cholesterol levels.

PROGRESS IN NEUROBIOLOGY (2021)

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Review Cell Biology

Hypertension-related risk for dementia: A summary review with future directions

Ana M. Daugherty

Summary: Chronic hypertension is the most prevalent vascular risk factor that accelerates cognitive aging and increases the risk for dementia. Successful blood pressure control improves outcomes, but does not completely eliminate the risk for dementia. Hypertension is associated with oxidative damage, systemic inflammation, and autonomic control of heart rate variability.

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY (2021)

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Review Geriatrics & Gerontology

Brain Ischemia as a Prelude to Alzheimer's Disease

Ryszard Pluta et al.

Summary: Transient ischemic brain injury results in massive neuronal death in the hippocampus and progressive atrophy of brain structures. Post-ischemic brain neurodegeneration can continue well beyond the acute stage and is associated with the deposition of folding proteins like amyloid and tau protein. Studies have shown dysregulation of Alzheimer's disease-associated genes in the development of post-ischemic brain neurodegeneration, suggesting a common pathway with Alzheimer's disease.

FRONTIERS IN AGING NEUROSCIENCE (2021)

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Article Immunology

T Cells Actively Infiltrate the White Matter of the Aging Monkey Brain in Relation to Increased Microglial Reactivity and Cognitive Decline

Katelyn V. Batterman et al.

Summary: Research suggests that myelin pathology in white matter during aging may be associated with infiltration of T cells, which in turn is linked to cognitive decline.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Neurosciences

Cerebrovascular damage after midlife transient hypertension in non-transgenic and Alzheimer's disease rats

Aaron Y. Lai et al.

Summary: Transient hypertension leads to cerebrovasculature and white matter damage, particularly affecting the cingulate cortex crucial for cognitive function. The combined effects of hypertension and AD genotype result in loss of cortical myelin. Vascular pathologies serve as pathological links to increased risk of dementia.

BRAIN RESEARCH (2021)

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Review Biochemistry & Molecular Biology

Cholesterol Dysmetabolism in Alzheimer's Disease: A Starring Role for Astrocytes?

Erica Staurenghi et al.

Summary: The impairment of cholesterol metabolism has been intensively investigated in the pathogenesis of Alzheimer's disease (AD), particularly the role of cholesterol oxidation products oxysterols. Astrocytes play a crucial role in maintaining brain cholesterol homeostasis, delivering cholesterol to neurons and modulating synaptic transmission. The morphological and functional changes of astrocytes in the AD brain contribute to the onset and development of AD, but the extent of this contribution and the role of oxysterols are still unclear.

ANTIOXIDANTS (2021)

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Article Multidisciplinary Sciences

Bacterial lipopolysaccharide is associated with stroke

Marisa Hakoupian et al.

Summary: Plasma levels of LPS and LBP are associated with major causes of ischemic stroke and ICH, but not with TIAs. LPS positively correlates with CRP and LBP levels, but negatively correlates with cholesterol. Higher LPS levels are associated with worse stroke outcomes.

SCIENTIFIC REPORTS (2021)

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Review Biochemistry & Molecular Biology

Apolipoprotein E isoform-dependent effects on the processing of Alzheimer's amyloid-β

Amanda B. Chai et al.

Summary: Research has shown a strong correlation between apoE4 and the risk of Alzheimer's disease, primarily due to increased brain Aβ burden, earlier disease onset, and worse clinical outcomes caused by apoE4. However, there is still debate on the effects of different apoE isoforms on various stages of the Aβ processing pathway, potentially reflecting inconsistencies in research methodologies.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS (2021)

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Article Clinical Neurology

Effect of High Cholesterol Regulation of LRP1 and RAGE on Aβ Trans-port Across the Blood-Brain Barrier in Alzheimer's Disease

Rui Zhou et al.

Summary: The study revealed that high cholesterol exacerbates cognitive impairment in AD mice by affecting A beta transport through decreasing LRP1 expression and increasing RAGE expression in cerebral microvascular endothelial cells, leading to increased brain apoptosis and worsened cognitive function.

CURRENT ALZHEIMER RESEARCH (2021)

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Article Clinical Neurology

The Absence of Myelin Basic Protein Reduces Non-Amyloidogenic Processing of Amyloid Precursor Protein

Chika Seiwa et al.

Summary: The study found a significant reduction in cerebral sAPP alpha levels in Shiverer (shi/shi) mice without MBP, while total APP and sAPP beta levels remained unchanged. This suggests that targeting myelin of oligodendrocytes may be a novel therapy for the prevention and treatment of AD.

CURRENT ALZHEIMER RESEARCH (2021)

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Article Neurosciences

Enhancing myelin renewal reverses cognitive dysfunction in a murine model of Alzheimer's disease

Jing-Fei Chen et al.

Summary: The study found a significant increase in new myelin formation rate in the APP/PS1 mouse model of Alzheimer's disease, despite a decrease in overall myelination levels in the cortex and hippocampus. Enhancing myelin renewal through genetic or pharmacological methods improved cognitive performance in memory-related tasks.

NEURON (2021)

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Review Chemistry, Multidisciplinary

Interactions of Lipids, Lipoproteins, and Apolipoproteins with the Blood-Brain Barrier

Elizabeth M. Rhea et al.

Summary: The interactions between lipids, lipoproteins, and apolipoproteins with the blood-brain barrier (BBB) are diverse and important for both health and disease.

PHARMACEUTICAL RESEARCH (2021)

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Article Multidisciplinary Sciences

Regulation of beta-amyloid production in neurons by cholesterol

Hao Wang et al.

Summary: The study shows that apoE uses astrocyte-derived cholesterol to traffic neuronal APP in and out of lipid clusters, generating A beta peptide. Deletion of astrocyte cholesterol synthesis reduces amyloid and tau burden in a mouse model of AD, indicating that cholesterol is kept low in neurons and astrocytes regulate A beta accumulation through cholesterol signaling.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Clinical Neurology

Loss and dispersion of superficial white matter in Alzheimer's disease: a diffusion MRI study

Thomas Veale et al.

Summary: Pathological cerebral white matter changes in Alzheimer's disease, particularly in the superficial white matter, were investigated using advanced diffusion MRI techniques in young-onset patients. The results showed decreased neurite density and increased orientation dispersion in the superficial white matter of young-onset Alzheimer's disease individuals, indicating both neurodegenerative and organizational changes. These findings suggest that standard diffusion tensor metrics may not capture the full extent of microstructural alterations in superficial white matter in Alzheimer's disease.

BRAIN COMMUNICATIONS (2021)

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Article Geriatrics & Gerontology

Abnormal brain cholesterol homeostasis in Alzheimer's disease-a targeted metabolomic and transcriptomic study

Vijay R. Varma et al.

Summary: The study reveals abnormalities in brain cholesterol biosynthesis and catabolism in patients with AD, leading to unstable cholesterol levels and accumulation of cytotoxic oxidized sterols. These changes were not observed in patients with Parkinson's disease, suggesting a specificity to AD.

NPJ AGING AND MECHANISMS OF DISEASE (2021)

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Review Neurosciences

Diffusion tensor imaging of white matter degeneration in early stage of Alzheimer's disease: a review

Viviana Lo Buono et al.

INTERNATIONAL JOURNAL OF NEUROSCIENCE (2020)

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Article Biochemistry & Molecular Biology

Brain region-specific amyloid plaque-associated myelin lipid loss, APOE deposition and disruption of the myelin sheath in familial Alzheimer's disease mice

Ibrahim Kaya et al.

JOURNAL OF NEUROCHEMISTRY (2020)

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Review Neurosciences

The multiplex model of the genetics of Alzheimer's disease

Rebecca Sims et al.

NATURE NEUROSCIENCE (2020)

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Article Multidisciplinary Sciences

An IL-18-centered inflammatory network as a biomarker for cerebral white matter injury

Marie Altendahl et al.

PLOS ONE (2020)

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Review Geriatrics & Gerontology

Proceedings from the Albert Charitable Trust Inaugural Workshop on white matter and cognition in aging

Farzaneh A. Sorond et al.

GEROSCIENCE (2020)

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Review Geriatrics & Gerontology

Revealing a Novel Landscape of the Association Between Blood Lipid Levels and Alzheimer's Disease: A Meta-Analysis of a Case-Control Study

Qianyun Tang et al.

FRONTIERS IN AGING NEUROSCIENCE (2020)

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Article Clinical Neurology

White matter alterations in Alzheimer's disease without concomitant pathologies

I Ferrer et al.

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY (2020)

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Article Cell Biology

APOE ε4 allele accelerates age-related multi-cognitive decline and white matter damage in non-demented elderly

Jinping Sun et al.

Aging-US (2020)

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Review Physiology

Involvement of Lipids in Alzheimer's Disease Pathology and Potential Therapies

Hannah Chew et al.

FRONTIERS IN PHYSIOLOGY (2020)

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Article Biophysics

Diffusion MRI detects early brain microstructure abnormalities in 2-month-old 3xTg-AD mice

Maria Fatima Falangola et al.

NMR IN BIOMEDICINE (2020)

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Article Biochemistry & Molecular Biology

The Alzheimer's disease-associated C99 fragment of APP regulates cellular cholesterol trafficking

Jorge Montesinos et al.

EMBO JOURNAL (2020)

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Article Geriatrics & Gerontology

Disruption of oligodendrocyte progenitor cells is an early sign of pathology in the triple transgenic mouse model of Alzheimer's disease

Ilaria Vanzulli et al.

NEUROBIOLOGY OF AGING (2020)

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Article Neurosciences

White matter hyperintensities are associated with subthreshold amyloid accumulation

Alexis Moscoso et al.

NEUROIMAGE (2020)

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Review Neurosciences

Demyelinating processes in aging and stroke in the central nervous system and the prospect of treatment strategy

Di Chen et al.

CNS NEUROSCIENCE & THERAPEUTICS (2020)

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Article Multidisciplinary Sciences

Oligodendroglial glycolytic stress triggers inflammasome activation and neuropathology in Alzheimer's disease

Xinwen Zhang et al.

SCIENCE ADVANCES (2020)

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Article Neurosciences

Longitudinal white matter and cognitive development in pediatric carriers of the apolipoprotein ε4 allele

Justin Remer et al.

NEUROIMAGE (2020)

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Article Medicine, General & Internal

The role of myelin damage in Alzheimer's disease pathology

Ewa Papuc et al.

ARCHIVES OF MEDICAL SCIENCE (2020)

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Article Clinical Neurology

Alzheimer-related altered white matter microstructural integrity in Down syndrome: A model for sporadic AD?

H. Diana Rosas et al.

ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING (2020)

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Review Biochemistry & Molecular Biology

Alterations in cholesterol metabolism as a risk factor for developing Alzheimer's disease: Potential novel targets for treatment

Ranl Loera-Valencia et al.

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY (2019)

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Article Biochemistry & Molecular Biology

Astaxanthin exerts protective effects similar to bexarotene in Alzheimer's disease by modulating amyloid-beta and cholesterol homeostasis in blood-brain barrier endothelial cells

Elham Fanaee-Danesh et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE (2019)

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Article Neurosciences

A Novel Apolipoprotein E Antagonist Functionally Blocks Apolipoprotein E Interaction With N-terminal Amyloid Precursor Protein, Reduces β-Amyloid-Associated Pathology, and Improves Cognition

Darrell Sawmiller et al.

BIOLOGICAL PSYCHIATRY (2019)

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Article Multidisciplinary Sciences

Single-cell transcriptomic analysis of Alzheimer's disease

Hansruedi Mathys et al.

NATURE (2019)

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Article Biochemistry & Molecular Biology

ABCA1-and ABCG1-mediated cholesterol efflux capacity of cerebrospinal fluid is impaired in Alzheimer's disease[S]

Cinzia Marchi et al.

JOURNAL OF LIPID RESEARCH (2019)

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Article Geriatrics & Gerontology

Lipopolysaccharide exposure in a rat sepsis model results in hippocampal amyloid-β plaque and phosphorylated tau deposition and corresponding behavioral deficits

Ryan A. Kirk et al.

GEROSCIENCE (2019)

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Article Clinical Neurology

The metalloprotease ADAMTS4 generates N-truncated A4-x species and marks oligodendrocytes as a source of amyloidogenic peptides in Alzheimer's disease

Susanne Walter et al.

ACTA NEUROPATHOLOGICA (2019)

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Article Cell Biology

Conditional Deletion of LRP1 Leads to Progressive Loss of Recombined NG2-Expressing Oligodendrocyte Precursor Cells in a Novel Mouse Model

Ina Schaefer et al.

CELLS (2019)

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Article Clinical Neurology

27-hydroxycholesterol promotes Aβ accumulation via altering Aβ metabolism in mild cognitive impairment patients and APP/PS1 mice

Xiaona Zhang et al.

BRAIN PATHOLOGY (2019)

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Review Neurosciences

A Crosstalk Between Brain Cholesterol Oxidation and Glucose Metabolism in Alzheimer's Disease

Paola Gamba et al.

FRONTIERS IN NEUROSCIENCE (2019)

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Article Neuroimaging

Interactive effect of age and APOE-epsilon 4 allele load on white matter myelin content in cognitively normal middle-aged subjects

Gregory Operto et al.

NEUROIMAGE-CLINICAL (2019)

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Article Oncology

High-cholesterol diet results in elevated amyloid- and oxysterols in rats

Quanri Liu et al.

MOLECULAR MEDICINE REPORTS (2018)

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Article Clinical Neurology

DNA damage-associated oligodendrocyte degeneration precedes amyloid pathology and contributes to Alzheimer's disease and dementia

Kai-Hei Tse et al.

ALZHEIMERS & DEMENTIA (2018)

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Article Clinical Neurology

Vasodilator Dysfunction and Oligodendrocyte Dysmaturation in Aging White Matter

Zsolt Bagi et al.

ANNALS OF NEUROLOGY (2018)

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Article Neurosciences

Myelin changes at the early stage of 5XFAD mice

Lihua Gu et al.

BRAIN RESEARCH BULLETIN (2018)

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Article Neurosciences

LINGO-1 antibody ameliorates myelin impairment and spatial memory deficits in the early stage of 5XFAD mice

Di Wu et al.

CNS NEUROSCIENCE & THERAPEUTICS (2018)

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Article Food Science & Technology

Increased Levels of 27-Hydroxycholesterol Induced by Dietary Cholesterol in Brain Contribute to Learning and Memory Impairment in Rats

Xiaona Zhang et al.

MOLECULAR NUTRITION & FOOD RESEARCH (2018)

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Article Chemistry, Multidisciplinary

Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes

Johnny Habchi et al.

NATURE CHEMISTRY (2018)

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Article Biochemistry & Molecular Biology

Pericyte degeneration causes white matter dysfunction in the mouse central nervous system

Axel Montagne et al.

NATURE MEDICINE (2018)

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Article Cell Biology

Association between Alzheimer's disease pathogenesis and early demyelination and oligodendrocyte dysfunction

Yu-Xia Dong et al.

NEURAL REGENERATION RESEARCH (2018)

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Article Neurosciences

Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury

Yi Yang et al.

NEUROBIOLOGY OF DISEASE (2018)

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Article Multidisciplinary Sciences

Defective cholesterol clearance limits remyelination in the aged central nervous system

Ludovico Cantuti-Castelvetri et al.

SCIENCE (2018)

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Article Clinical Neurology

White matter microstructure is altered in cognitively normal middle-aged APOE-ε4

Gregory Operto et al.

ALZHEIMERS RESEARCH & THERAPY (2018)

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Review Geriatrics & Gerontology

Lipopolysaccharide Associates with Amyloid Plaques, Neurons and Oligodendrocytes in Alzheimer's Disease Brain: A Review

Xinhua Zhan et al.

FRONTIERS IN AGING NEUROSCIENCE (2018)

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Review Neurosciences

White matter changes in Alzheimer's disease: a focus on myelin and oligodendrocytes

Sara E. Nasrabady et al.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2018)

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Article Clinical Neurology

White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer's disease

Miguel Angel Araque Caballero et al.

BRAIN (2018)

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Article Clinical Neurology

White matter involvement in young non-demented Down's syndrome subjects: a tract-based spatial statistic analysis

Andrea Romano et al.

NEURORADIOLOGY (2018)

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Article Neurosciences

Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism

Qingyi Ma et al.

MOLECULAR NEURODEGENERATION (2018)

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Review Oncology

Overview the effect of statin therapy on dementia risk, cognitive changes and its pathologic change: a systematic review and meta-analysis

Xi-Chen Zhu et al.

ANNALS OF TRANSLATIONAL MEDICINE (2018)

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Article Neurosciences

3D Tract-Specific Local and Global Analysis of White Matter Integrity in Alzheimer's Disease

Yan Jin et al.

HUMAN BRAIN MAPPING (2017)

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Article Neurosciences

Reduced Cardiovascular Functions in Patients with Alzheimer's Disease

Wang-Sheng Jin et al.

JOURNAL OF ALZHEIMERS DISEASE (2017)

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Article Biochemistry & Molecular Biology

The Research on the Relationship of RAGE, LRP-1, and Aβ Accumulation in the Hippocampus, Prefrontal Lobe, and Amygdala of STZ-Induced Diabetic Rats

Lou-Yan Ma et al.

JOURNAL OF MOLECULAR NEUROSCIENCE (2017)

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Article Biochemistry & Molecular Biology

Diabetes alters myelin lipid profile in rat cerebral cortex: Protective effects of dihydroprogesterone

Gaia Cermenati et al.

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY (2017)

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Article Geriatrics & Gerontology

Age-related white matter integrity differences in oldest-old without dementia

Ilana J. Bennett et al.

NEUROBIOLOGY OF AGING (2017)

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Article Geriatrics & Gerontology

Aging alters mRNA expression of amyloid transporter genes at the blood-brain barrier

Doreen Osgood et al.

NEUROBIOLOGY OF AGING (2017)

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Article Neurosciences

Alterations of myelin morphology and oligodendrocyte development in early stage of Alzheimer's disease mouse model

Yu Wu et al.

NEUROSCIENCE LETTERS (2017)

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Article Biology

LRP1 regulates peroxisome biogenesis and cholesterol homeostasis in oligodendrocytes and is required for proper CNS myelin development and repair

Jing-Ping Lin et al.

ELIFE (2017)

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Article Multidisciplinary Sciences

Microstructural white matter alterations in preclinical Alzheimer's disease detected using free water elimination diffusion tensor imaging

Andrew R. Hoy et al.

PLOS ONE (2017)

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Article Multidisciplinary Sciences

Expression and function of Abcg4 in the mouse blood-brain barrier: role in restricting the brain entry of amyloid-β peptide

Agnes Dodacki et al.

SCIENTIFIC REPORTS (2017)

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Article Medicine, Research & Experimental

Thymoquinone-rich fraction nanoemulsion (TQRFNE) decreases Aβ40 and Aβ42 levels by modulating APP processing, up-regulating IDE and LRP1, and down-regulating BACE1 and RAGE in response to high fat/cholesterol diet-induced rats

Norsharina Ismail et al.

BIOMEDICINE & PHARMACOTHERAPY (2017)

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Article Clinical Neurology

Brain Microvascular Injury and White Matter Disease Provoked by Diabetes-Associated Hyperamylinemia

Han Ly et al.

ANNALS OF NEUROLOGY (2017)

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Article Clinical Neurology

Exercise Prevents Cognitive Function Decline and Demyelination in the White Matter of APP/PS1 Transgenic AD Mice

Lei Zhang et al.

CURRENT ALZHEIMER RESEARCH (2017)

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Review Cell Biology

Aging of cerebral white matter

Huan Liu et al.

AGEING RESEARCH REVIEWS (2017)

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Review Neurosciences

Oligodendrocytes and Alzheimer's disease

Zhiyou Cai et al.

INTERNATIONAL JOURNAL OF NEUROSCIENCE (2016)

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Article Neurosciences

ABCA1 is Necessary for Bexarotene-Mediated Clearance of Soluble Amyloid Beta from the Hippocampus of APP/PS1 Mice

Angela W. Corona et al.

JOURNAL OF NEUROIMMUNE PHARMACOLOGY (2016)

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Review Clinical Neurology

Risk factors for predicting progression from mild cognitive impairment to Alzheimer's disease: a systematic review and meta-analysis of cohort studies

Jie-Qiong Li et al.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2016)

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Article Clinical Neurology

White Matter Hyperintensities Are a Core Feature of Alzheimer's Disease: Evidence from the Dominantly Inherited Alzheimer Network

Seonjoo Lee et al.

ANNALS OF NEUROLOGY (2016)

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Review Medicine, Research & Experimental

The amyloid hypothesis of Alzheimer's disease at 25years

Dennis J. Selkoe et al.

EMBO MOLECULAR MEDICINE (2016)

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Article Chemistry, Physical

Specific Binding of Cholesterol to C99 Domain of Amyloid Precursor Protein Depends Critically on Charge State of Protein

Afra Panahi et al.

JOURNAL OF PHYSICAL CHEMISTRY LETTERS (2016)

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Article Geriatrics & Gerontology

Cerebral amyloid is associated with greater white-matter hyperintensity accrual in cognitively normal older adults

Julia A. Scott et al.

NEUROBIOLOGY OF AGING (2016)

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Article Geriatrics & Gerontology

Loss of ceramide synthase 2 activity, necessary for myelin biosynthesis, precedes tau pathology in the cortical pathogenesis of Alzheimer's disease

Timothy A. Couttas et al.

NEUROBIOLOGY OF AGING (2016)

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Article Clinical Neurology

Gram-negative bacterial molecules associate with Alzheimer disease pathology

Xinhua Zhan et al.

NEUROLOGY (2016)

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Review Neurosciences

Age-specific localization of NMDA receptors on oligodendrocytes dictates axon function recovery after ischemia

Selva Baltan

NEUROPHARMACOLOGY (2016)

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Article Clinical Neurology

Widespread white matter degeneration preceding the onset of dementia

Klaus H. Maier-Hein et al.

ALZHEIMERS & DEMENTIA (2015)

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Article Clinical Neurology

Loss-of-function mutation in ABCA1 and risk of Alzheimer's disease and cerebrovascular disease

Liv Tybjaerg Nordestgaard et al.

ALZHEIMERS & DEMENTIA (2015)

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Article Behavioral Sciences

27-Hydroxycholesterol mediates negative effects of dietary cholesterol on cognition in mice

Maura Heverin et al.

BEHAVIOURAL BRAIN RESEARCH (2015)

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Review Biochemistry & Molecular Biology

Cholesterol in myelin biogenesis and hypomyelinating disorders

Gesine Saher et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS (2015)

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Article Clinical Neurology

CYP46A1 inhibition, brain cholesterol accumulation and neurodegeneration pave the way for Alzheimer's disease

Fathia Djelti et al.

BRAIN (2015)

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Article Clinical Neurology

Running Exercise Reduces Myelinated Fiber Loss in the Dentate Gyrus of the Hippocampus in APP/PS1 Transgenic Mice

Fenglei Chao et al.

CURRENT ALZHEIMER RESEARCH (2015)

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Article Biochemistry & Molecular Biology

Cholesterol 24-hydroxylase defect is implicated in memory impairments associated with Alzheimer-like Tau pathology

Marie-Anne Burlot et al.

HUMAN MOLECULAR GENETICS (2015)

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Article Neurosciences

Cholestenoic acid, an endogenous cholesterol metabolite, is a potent γ-secretase modulator

Joo In Jung et al.

MOLECULAR NEURODEGENERATION (2015)

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Article Neurosciences

The case for rejecting the amyloid cascade hypothesis

Karl Herrup

NATURE NEUROSCIENCE (2015)

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Article Geriatrics & Gerontology

The N-terminal region of myelin basic protein reduces fibrillar amyloid-β deposition in Tg-5xFAD mice

Ming-Hsuan Ou-Yang et al.

NEUROBIOLOGY OF AGING (2015)

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Article Neurosciences

27-HYDROXYCHOLESTEROL CONTRIBUTES TO DISRUPTIVE EFFECTS ON LEARNING AND MEMORY BY MODULATING CHOLESTEROL METABOLISM IN THE RAT BRAIN

D. -D. Zhang et al.

NEUROSCIENCE (2015)

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Article Geriatrics & Gerontology

Cerebral Amyloid and Hypertension are Independently Associated with White Matter Lesions in Elderly

Julia A. Scott et al.

FRONTIERS IN AGING NEUROSCIENCE (2015)

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Review Geriatrics & Gerontology

Oxidized cholesterol as the driving force behind the development of Alzheimer's disease

Paola Gamba et al.

FRONTIERS IN AGING NEUROSCIENCE (2015)

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Article Neuroimaging

Altered whole-brain white matter networks in preclinical Alzheimer's disease

Florian Udo Fischer et al.

NEUROIMAGE-CLINICAL (2015)

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Review Neurosciences

The Role of Cholesterol Metabolism in Alzheimer's Disease

Jia-Hao Sun et al.

MOLECULAR NEUROBIOLOGY (2015)

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Article Clinical Neurology

Aggregation of MBP in chronic demyelination

Kati Frid et al.

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY (2015)

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Article Neurosciences

Inflammation Combined with Ischemia Produces Myelin Injury and Plaque-Like Aggregates of Myelin, Amyloid-β and AβPP in Adult Rat Brain

Xinhua Zhan et al.

JOURNAL OF ALZHEIMERS DISEASE (2015)

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Review Geriatrics & Gerontology

Interactive Effects of Apolipoprotein E4 and Diabetes Risk on Later Myelinating White Matter Regions in Neurologically Healthy Older Aged Adults

Jessica M. Foley et al.

AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS (2014)

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Article Clinical Neurology

Myelin Injury and Degraded Myelin Vesicles in Alzheimer's Disease

Xinhua Zhan et al.

CURRENT ALZHEIMER RESEARCH (2014)

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Article Biochemistry & Molecular Biology

Effects of a Disrupted Blood-Brain Barrier on Cholesterol Homeostasis in the Brain

Ahmed A. Saeed et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2014)

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Review Geriatrics & Gerontology

Apolipoprotein E and lipid homeostasis in the etiology and treatment of sporadic Alzheimer's disease

Judes Poirier et al.

NEUROBIOLOGY OF AGING (2014)

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Article Geriatrics & Gerontology

White matter changes in preclinical Alzheimer's disease: a magnetic resonance imaging-diffusion tensor imaging study on cognitively normal older people with positive amyloid β protein 42 levels

Jose Luis Molinuevo et al.

NEUROBIOLOGY OF AGING (2014)

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Article Geriatrics & Gerontology

Serum cholesterol and variant in cholesterol-related gene CETP predict white matter microstructure

Nicholus M. Warstadt et al.

NEUROBIOLOGY OF AGING (2014)

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Article Neurosciences

Apolipoprotein E Isoform-Specific Effects on Lipoprotein Receptor Processing

Corbin Bachmeier et al.

NEUROMOLECULAR MEDICINE (2014)

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Review Neurosciences

ApoE and Aβ in Alzheimer's Disease: Accidental Encounters or Partners?

Takahisa Kanekiyo et al.

NEURON (2014)

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Article Clinical Neurology

Associations Between Serum Cholesterol Levels and Cerebral Amyloidosis

Bruce Reed et al.

JAMA NEUROLOGY (2014)

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Article Clinical Neurology

Brain Differences in Infants at Differential Genetic Risk for Late-Onset Alzheimer Disease A Cross-sectional Imaging Study

Douglas C. Dean et al.

JAMA NEUROLOGY (2014)

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Article Neurosciences

Soluble amyloid beta levels are elevated in the white matter of Alzheimer's patients, independent of cortical plaque severity

Lyndsey E. Collins-Praino et al.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2014)

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Article Biochemistry & Molecular Biology

Biochemical Identification of a Linear Cholesterol-Binding Domain within Alzheimer's β Amyloid Peptide

Coralie Di Scala et al.

ACS CHEMICAL NEUROSCIENCE (2013)

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Article Pharmacology & Pharmacy

Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer's disease

Julius Popp et al.

BIOCHEMICAL PHARMACOLOGY (2013)

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Article Biochemistry & Molecular Biology

Fine Mapping of the Amyloid β-Protein Binding Site on Myelin Basic Protein

AnnMarie E. Kotarba et al.

BIOCHEMISTRY (2013)

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Article Biochemistry & Molecular Biology

Cholesterol efflux is differentially regulated in neurons and astrocytes: Implications for brain cholesterol homeostasis

Jing Chen et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS (2013)

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Article Pharmacology & Pharmacy

Probucol prevents blood-brain barrier dysfunction in wild-type mice induced by saturated fat or cholesterol feeding

Ryusuke Takechi et al.

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY (2013)

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Article Clinical Neurology

Characterization of Myelin Pathology in the Hippocampal Complex of a Transgenic Mouse Model of Alzheimer’s Disease

Larry C. Schmued et al.

Current Alzheimer Research (2013)

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Review Psychiatry

Is Alzheimer's a disease of the white matter?

Perminder S. Sachdev et al.

CURRENT OPINION IN PSYCHIATRY (2013)

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Review Clinical Neurology

White matter abnormalities associated with Alzheimer's disease and mild cognitive impairment: a critical review of MRI studies

Marcia Radanovic et al.

EXPERT REVIEW OF NEUROTHERAPEUTICS (2013)

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Article Medicine, Research & Experimental

Hypercholesterolemia accelerates amyloid β-induced cognitive deficits

Sun Haeng Park et al.

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE (2013)

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Article Immunology

The absence of myelin basic protein promotes neuroinflammation and reduces amyloid β-protein accumulation in Tg-5xFAD mice

Ming-Hsuan Ou-Yang et al.

JOURNAL OF NEUROINFLAMMATION (2013)

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Article Geriatrics & Gerontology

White matter microstructural damage in Alzheimer's disease at different ages of onset

Elisa Canu et al.

NEUROBIOLOGY OF AGING (2013)

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Article Multidisciplinary Sciences

ApoE influences amyloid-β (Aβ) clearance despite minimal apoE/Aβ association in physiological conditions

Philip B. Verghese et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

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Article Radiology, Nuclear Medicine & Medical Imaging

Symptomatic White Matter Changes in Mild Traumatic Brain Injury Resemble Pathologic Features of Early Alzheimer Dementia

Saeed Fakhran et al.

RADIOLOGY (2013)

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Article Geriatrics & Gerontology

Antioxidant Status and APOE Genotype As Susceptibility Factors for Neurodegeneration in Alzheimer's Disease and Vascular Dementia

Giancarlo Zito et al.

REJUVENATION RESEARCH (2013)

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Article Clinical Neurology

Age-Related Decline in Oligodendrogenesis Retards White Matter Repair in Mice

Nobukazu Miyamoto et al.

STROKE (2013)

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Review Clinical Neurology

Evidence for impaired amyloid beta clearance in Alzheimer's disease

Kristin R. Wildsmith et al.

ALZHEIMERS RESEARCH & THERAPY (2013)

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Article Clinical Neurology

Loss of Fornix White Matter Volume as a Predictor of Cognitive Impairment in Cognitively Normal Elderly Individuals

Evan Fletcher et al.

JAMA NEUROLOGY (2013)

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Review Physiology

The role of ABCB1 and ABCA1 in beta-amyloid clearance at the neurovascular unit in Alzheimer's disease

Ayman ElAli et al.

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Amyloid β1-42 oligomer inhibits myelin sheet formation in vitro

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Multiple Diffusion Indices Reveals White Matter Degeneration in Alzheimer's Disease and Mild Cognitive Impairment: A Tract-Based Spatial Statistics Study

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Higher Incidence of Mild Cognitive Impairment in Familial Hypercholesterolemia

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Early Oligodendrocyte/Myelin Pathology in Alzheimer's Disease Mice Constitutes a Novel Therapeutic Target

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Multiple indicators of age-related differences in cerebral white matter and the modifying effects of hypertension

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Alterations in multiple measures of white matter integrity in normal women at high risk for Alzheimer's disease

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ACAT1 gene ablation increases 24(S)-hydroxycholesterol content in the brain and ameliorates amyloid pathology in mice with AD

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Myelin Basic Protein Binds to and Inhibits the Fibrillar Assembly of Aβ42 in Vitro

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Lipopolysaccharide alters the blood-brain barrier transport of amyloid β protein: A mechanism for inflammation in the progression of Alzheimer's disease

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Triple-Transgenic Alzheimer's Disease Mice Exhibit Region-Specific Abnormalities in Brain Myelination Patterns Prior to Appearance of Amyloid and Tau Pathology

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Regulated Proteolysis of RAGE and A beta PP as Possible Link Between Type 2 Diabetes Mellitus and Alzheimer's Disease

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LRP1 Controls Intracellular Cholesterol Storage and Fatty Acid Synthesis through Modulation of Wnt Signaling

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Degradation of Amyloid β Protein by Purified Myelin Basic Protein

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Low-density lipoprotein receptor-related protein 1 is an essential receptor for myelin phagocytosis

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Cholesterol metabolism and transport in the pathogenesis of Alzheimer's disease

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Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study

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LRP1 Controls cPLA2 Phosphorylation, ABCA1 Expression and Cellular Cholesterol Export

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Site-specific modification of Alzheimer's peptides by cholesterol oxidation products enhances aggregation energetics and neurotoxicity

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White matter damage and hippocampal neurodegeneration induced by permanent bilateral occlusion of common carotid artery in the rat: Comparison between Wistar and Sprague-Dawley strain

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Regulation of β-amyloid levels in the brain of cholesterol-fed rabbit, a model system for sporadic Alzheimer's disease

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Apolipoprotein e affects both myelin breakdown and cognition: Implications for age-related trajectories of decline into dementia

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Brain-to-blood elimination of 24S-hydroxycholesterol from rat brain is mediated by organic anion transporting polypeptide 2 (oatp2) at the blood-brain barrier

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Amyloid precursor protein regulates brain apolipoprotein e and cholesterol metabolism through lipoprotein receptor LRP1

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Diffusion tensor imaging in preclinical and presymptomatic carriers of familial Alzheimer's disease mutations

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Lower cardiac output is associated with greater white matter hyperintensities in older adults with cardiovascular disease

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Role of ABCG1 and ABCA1 in regulation of neuronal cholesterol efflux to apolipoprotein E discs and suppression of amyloid-β peptide generation

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Convergence of genes implicated in Alzheimer's disease on the cerebral cholesterol shuttle: APP, cholesterol, lipoproteins, and atherosclerosis

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High cholesterol content in neurons increases BACE, β-amyloid, and phosphorylated tau levels in rabbit hippocampus

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Role of cholesterol in amyloid cascade: cholesterol-dependent modulation of tau phosphorylation and mitochondrial function

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Oxysterols and Alzheimer's disease

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Lack of ABCA1 considerably decreases brain ApoE level and increases amyloid deposition in APP23 mice

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High cholesterol diet induces tau hyperphosphorylation in apolipoprotein E deficient mice

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Decreasing myelin density reflected increasing white matter pathology in Alzheimer's disease -: a neuropathological study

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Abnormal white matter integrity in healthy apolipoprotein E epsilon4 carriers

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Amyloid-β peptide enhances tumor necrosis factor-α-induced NOS through neutral sphingomyelinase/ceramide pathway in oligodendrocytes

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LPS receptor (CD14): a receptor for phagocytosis of Alzheimer's amyloid peptide

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BRAIN (2005)

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The link between cholesterol and Alzheimer's disease

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Meta-analysis of nonsteroidal antiinflammatory drug use and risk of dementia

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Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2004)

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Amyloid-β peptide induces oligodendrocyte death by activating the neutral sphingomyelinase-ceramide pathway

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Differential expression of cholesterol hydroxylases in Alzheimer's disease

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Heterogeneous age-related breakdown of white matter structural integrity: implications for cortical disconnection in aging and Alzheimer's diesase

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Experimental cerebral hypoperfusion induces white matter injury and microglial activation in the rat brain

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Two apolipoprotein E mimetic peptides, ApoE(130-149) and ApoE(141-155)2, bind to LRP1

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The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer's disease

B Hutter-Paier et al.

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Role of acyl-coenzyme A - Cholesterol acyltransferase activity in the processing of the amyloid precursor protein

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Brain cholesterol:: Long secret life behind a barrier

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Association between apolipoprotein E e4 allele and arteriosclerosis, cerebral amyloid angiopathy, and cerebral white matter damage in Alzheimer's disease

J Tian et al.

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Apolipoprotein E binding to low density lipoprotein receptor-related protein-1 inhibits cell migration via activation of cAMP-dependent protein kinase A

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Amyloid β peptide-induced corpus callosum damage and glial activation in vivo

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White matter structural integrity in healthy aging adults and patients with Alzheimer disease - A magnetic resonance imaging study

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Increased brain beta-amyloid load, phosphorylated tau, and risk of Alzheimer disease associated with an intronic CYP46 polymorphism

A Papassotiropoulos et al.

ARCHIVES OF NEUROLOGY (2003)

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Presenilin-1 mutation sensitizes oligodendrocytes to glutamate and amyloid toxicities, and exacerbates white matter damage and memory impairment in mice

K Pak et al.

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Blood-brain barrier permeability precedes senile plaque formation in an Alzheimer disease model

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ABCA1 and scavenger receptor class B, type I, are modulators of reverse sterol transport at an in Vitro blood-brain barrier constituted of porcine brain capillary endothelial cells

U Panzenboeck et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2002)

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Proton magnetic resonance spectroscopy reveals similar white matter biochemical changes in patients with chronic hypertension and early Alzheimer's disease

M Catani et al.

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Increased Aβ peptides and reduced cholesterol and myelin proteins characterize white matter degeneration in Alzheimer's disease

AE Roher et al.

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Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease: potential role in disease pathogenesis

XL Han et al.

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Diet-induced hypercholesterolemia enhances brain Aβ accumulation in transgenic mice

FS Shie et al.

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ApoE deficiency compromises the blood brain barrier especially after injury

N Methia et al.

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Acyl-coenzyme A:cholesterol acyltransferase modulates the generation of the amyloid β-peptide

L Puglielli et al.

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Cholesterol accumulates in senile plaques of Alzheimer disease patients and in transgenic APPsw mice

T Mori et al.

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY (2001)

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Apolipoprotein E protects against neuropathology induced by a high-fat diet and maintains the integrity of the blood-brain barrier during aging

M Mulder et al.

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Impairment of the blood-nerve and blood-brain barriers in apolipoprotein E knockout mice

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Review Biochemistry & Molecular Biology

Cholesterol metabolism in the brain

JM Dietschy et al.

CURRENT OPINION IN LIPIDOLOGY (2001)

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Amyloid-beta peptides are cytotoxic to oligodendrocytes

J Xu et al.

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Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model

LM Refolo et al.

NEUROBIOLOGY OF DISEASE (2000)

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