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Review
Biochemistry & Molecular Biology
Saffire H. Krance et al.
Summary: The study found that concentrations of clusterin and complement component 3 were significantly higher in the cerebrospinal fluid of Alzheimer's disease patients, while C-reactive protein concentrations were elevated in peripheral blood. The results collectively support elevated complement pathway activity in AD, characterized by increased CSF clusterin concentrations and inconsistently reflected by peripheral blood proteins related to an AD diagnosis.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Nipun Chopra et al.
Summary: The study found that miR-298 may have potential therapeutic effects on Alzheimer's disease by inhibiting the expression of key proteins and influencing posttranslational levels of tau protein. This research opens up new possibilities for miR-298 to become a target for Alzheimer's disease therapy.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Roy Chun-Laam Ng et al.
Summary: The decrease in circulating adiponectin levels is associated with neurodegeneration, neuroinflammation, and Alzheimer's disease pathologies. Increasing adiponectin through treatments like adipoRon can improve neuronal insulin signaling, memory functions, and reduce amyloid levels in Alzheimer's disease models.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Dara L. Dickstein et al.
Summary: Traumatic brain injury is a risk factor for neurodegenerative diseases, particularly chronic traumatic encephalopathy. This study identified biomarker signatures associated with chronic anxiety traits and behavioral, cognitive, and memory complaints in individuals exposed to blast injuries.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Joseph Therriault et al.
Summary: Through analysis of three independent samples of cognitively unimpaired, mild cognitive impairment, and Alzheimer's disease subjects, the study found that the interaction effect between APOE epsilon 4 and amyloid-beta was related to increased tau load in Alzheimer's disease-vulnerable regions. The interaction between one APOE epsilon 4 allele and amyloid-beta led to increased tau load, while the interaction between amyloid-beta and two APOE epsilon 4 alleles was associated with a more widespread pattern of tau aggregation.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
May A. Beydoun et al.
Summary: The study suggests that co-infection between Helicobacter pylori and specific periodontal pathogens may alter the onset of Alzheimer's disease and all-cause dementia. Certain periodontal pathogens interact synergistically or antagonistically with Hp sero-positivity, affecting the risk of both types of dementia.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Yin Xu et al.
Summary: The transcription factor EB (TFEB) plays a crucial role in the lysosomal exocytosis of selected tau species, with TFEB loss causing a decrease in tau levels and accelerated spreading within neurons. This suggests that TFEB-mediated tau exocytosis acts as a clearance mechanism to reduce intracellular tau levels under pathological conditions.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Anne Nitsche et al.
Summary: Alzheimer's disease is a neurodegenerative disorder that predominantly affects elderly humans, with little occurrence in non-primate mammals and non-human primates. Research shows that most AD-associated genes have ancient evolutionary origins, but exhibit faster gene structure evolution in loci with AD-related expression changes. Particularly, non-coding genes associated with AD play a significant role in the disease.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
H. Stocker et al.
Summary: The study found that the AD polygenic risk score (PRS) and APOE status could effectively predict the clinical diagnosis of AD, VD, MD, and all-cause dementia in a community-based cohort.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Daniela Monteiro-Fernandes et al.
Summary: Despite progress in understanding AD neuropathology, there is no effective treatment for the memory deficits caused by A beta and Tau protein accumulation. However, positive allosteric modulation of AMPA receptors shows promise in restoring memory and synaptic signaling in non-transgenic animal models.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Swagata Ghatak et al.
Summary: Early stages of human Alzheimer's disease (AD) show hyperexcitability in the brain, leading to extensive synapse loss and cognitive dysfunction, with no current disease-modifying therapy available. Utilizing human iPSC models may be a valuable tool for screening drugs to treat hyperexcitability and synaptic damage in AD, potentially increasing the chances of success in treatment.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Rowan Pentz et al.
Summary: The study revealed that in Alzheimer's disease, there are changes in the metabolism of NGF, leading to disease progression. Mature NGF degradation is enhanced while proNGF maturation is impaired, with these changes correlating with cognition, pathology, and cholinergic tone.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Min Su Kang et al.
Summary: The study found that increased NFL concentrations in cerebrospinal fluid (CSF) and plasma were associated with reduced grey matter density in vulnerable brain regions in Alzheimer's disease patients and transgenic rats. These results support the utility of NFL as a neuronal injury biomarker.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Maria Jose Perez et al.
Summary: Mutations in the PITRM1 gene lead to a slow-progressing syndrome characterized by cerebellar ataxia and cognitive decline. Studies using PITRM1-knockout iPSCs show induction of mitochondrial unfolded protein response and increased mitochondrial clearance in neurons, as well as elevated levels of amyloid precursor protein and amyloid beta. Astrocytes also show dysregulated immune transcriptional signatures in PITRM1-knockout cerebral organoids.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Antoinette O'Connor et al.
Summary: Blood biomarker p-tau181 shows increased concentration in symptomatic and presymptomatic carriers of familial AD, with individual values able to differentiate carriers from non-carriers of the same age and sex. A fitted model suggests that p-tau181 concentrations were higher in mutation carriers than non-carriers from 16 years prior to estimated symptom onset.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Sho Moriguchi et al.
Summary: The study found that tau protein accumulations in the brains of MDD patients were significantly higher than healthy controls, especially in patients with psychotic symptoms. These findings suggest that tau depositions may underlie MDD, particularly in those with psychotic symptoms.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Hao-Lun Sun et al.
Summary: The study demonstrated the significant contribution of blood cell-produced A beta to the pathogenesis of AD, and eliminating peripheral A beta production can reduce brain A beta deposition, presenting a novel therapeutic approach for AD.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Laetitia Lemoine et al.
Summary: This study demonstrates differences in the properties of amyloid plaques between two genetic variants of AD and sAD. Despite the lack of measurable amyloid fibrils in AβPP mutation carriers, high regional tau and astrocyte binding were observed. Differences in the pathological cascade between AD variants were suggested, warranting further exploration in vivo.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Konstantinos Chiotis et al.
Summary: This study suggests that baseline [F-18]THK5317 binding in temporal areas is accurate in predicting future cognitive decline in patients with AD spectrum, and is strongly associated with the rate of cognitive decline. Other baseline biomarkers were less accurate in prediction and not associated with the rate of cognitive decline.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Ivan Alic et al.
Summary: Research has shown that individuals with Down Syndrome exhibit Alzheimer's disease-like pathological changes, which can be successfully replicated in vitro cerebral organoids models. These findings suggest that DS cerebral organoids could serve as a potential detector for pre-morbid AD-risk populations, as well as a system for hypothesis-free drug screening and identification of natural suppressor genes for neurodegenerative diseases.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Jose Henrique Ledo et al.
Summary: Microglia containing phospho-deficient mutant PS1 show a slower kinetic response to brain micro injury in vivo and an inability to degrade A beta oligomers, leading to severe A beta accumulation in microglia in an Alzheimer's mouse model. This demonstrates a novel mechanism by which PS1 modulates microglial function and contributes to Alzheimer's-associated phenotypes.
MOLECULAR PSYCHIATRY
(2021)
Correction
Biochemistry & Molecular Biology
Fanny Eysert et al.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Yiyuan Xia et al.
Summary: C/EBP beta serves as a crucial transcription factor for temporally regulating APOE gene expression, modulating the role of ApoE4 in Alzheimer's disease pathogenesis. It promotes ApoE expression in the brain and accelerates AD pathologies.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Arianna Sala et al.
Summary: Mismatch between CSF and PET amyloid-beta biomarkers is common in preclinical/prodromal Alzheimer's disease individuals, with discordant biomarkers indicating elevated risk of progression towards fully abnormal amyloid-beta biomarkers. Biomarker discordance may lead to different genetic profiles and rates of amyloid-beta accumulation, suggesting distinct pathways towards established amyloid-beta pathology. This highlights the potential implications for the use of CSF and PET amyloid-beta biomarkers in clinical trials.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Jean Wu et al.
Summary: IL33 is essential for regulating the expression of AQP4 in astrocytes, with its deficiency leading to abnormal tau accumulation in neurons and impaired drainage. This study suggests that different forms of AQP4 play distinct roles in glymphatic drainage, with p-AQP4 driving flow toward perivenous space while n-AQP4 may help remove neuronal wastes. Defects in IL33-related mechanisms may contribute to chronic neurodegeneration and tauopathy in aging mice.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Xuechao Fei et al.
Summary: The dysregulation of formaldehyde (FA) is associated with the development of Alzheimer's Disease (AD), with elevated FA levels in AD patients and animal models leading to impaired cognitive functions. By degrading FA and promoting Aβ clearance, it is possible to reduce Aβ aggregation, improve neurotoxicity, and enhance cognitive function.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Jisu Park et al.
Summary: The study reveals that aberrantly activated anaplastic lymphoma kinase (ALK) is a key factor contributing to the pathology of Alzheimer's disease (AD), by inducing abnormal accumulation of tau protein and causing dysfunction in neurons. The research demonstrates that ALK disrupts autophagosome maturation, leading to tau accumulation and aggregation, ultimately resulting in neuronal dysfunction in AD.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Marco Bucci et al.
Summary: It is important to find biomarkers for early detection of Alzheimer's disease. This study compared cerebrospinal fluid and imaging biomarkers to predict cognitive decline in Alzheimer's patients. The results showed that PET tau was superior to CSF p-Tau181 and PET amyloid-beta in predicting cognitive decline.
MOLECULAR PSYCHIATRY
(2021)
Correction
Biochemistry & Molecular Biology
H. Stocker et al.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Matias Wagner et al.
Summary: Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. A study involving 509 FTD patients in Germany identified pathogenic variants in genes such as C9orf72, GRN, and MAPT. TBK1-associated FTD was found to be relatively common, and a homozygous missense variant in CTSF was confirmed as a new FTD gene.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Andrew G. B. Thompson et al.
Summary: Plasma tau and NfL show potential as biomarkers for prion disease, with diagnostic value in distinguishing disease types and clinical relevance in disease progression. In asymptomatic PRNP mutation carriers, plasma NfL levels start to rise years before symptom onset, indicating potential as a marker for disease onset.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Nicholas Brookhouser et al.
Summary: The study revealed that the APOE2 variant reduces the risk of developing Alzheimer's disease and showed that converting APOE3 to APOE2 significantly decreased the production of amyloid-beta peptides. Furthermore, it was demonstrated that the protective effects of APOE2 may be related to a mechanism involving non-amyloidogenic processing.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Ding-Yuan Tian et al.
Summary: This study investigated the impact of unilateral nephrectomy on Aβ clearance in both humans and animals, finding that the kidney plays a physiological role in clearing Aβ. Furthermore, chronic furosemide treatment was shown to reduce Aβ levels in the blood and brain, attenuate AD pathologies, and improve cognitive deficits in APP/PS1 mice. These findings suggest that facilitation of Aβ clearance via the kidney could be a novel potential therapeutic approach for AD.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Woo-In Ryu et al.
Summary: The study found that neural progenitor cells and astrocytes differentiated from induced pluripotent stem cells of late-onset Alzheimer's disease patients exhibit multiple inter-related bioenergetic alterations, including changes in mitochondrial respiration, reduced levels of NAD/NADH, and diminished glucose uptake. These findings suggest that Alzheimer's disease may involve multiple hits and innate inefficient cellular energy management.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Amit Kumar et al.
Summary: The study demonstrates that the novel astrocytic PET ligand BU99008 can visualize reactive astrogliosis in postmortem AD brains and proposes a multiple binding site model for different ligands in AD and control brains. The data shows significant differences in the proportion and affinities of binding sites between AD and control groups, indicating potential targets for future research.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Michael Wainberg et al.
Summary: Recent studies have reignited interest in the hypothesis that infectious agents, particularly herpesviruses, may contribute to Alzheimer's disease pathogenesis. These studies suggest that many key features of Alzheimer's disease, like amyloid beta production and neuroinflammation, may actually be protective responses to acute infection that become maladaptive in the case of chronic infection.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Rodrigo Morales et al.
Summary: This study demonstrates that administration of Aβ seeds through various peripheral routes can accelerate the accumulation of Aβ in the brains of AD mouse models. Oral administration of brain extracts had no impact on brain pathology. The peripheral administration of Aβ seeds led to the generation of a large proportion of aggregates in blood vessels, suggesting a role of vascular transport in AD-related pathological changes.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Andrew Tsatsanis et al.
Summary: Amyloidogenic processing of the amyloid precursor protein leads to the formation of amyloid-beta peptide plaques in Alzheimer's disease. Early cortical changes in AD also involve neuroinflammation and elevated iron levels. The activation of the innate immune system in the brain is a neuroprotective response to infection, but persistent neuroinflammation is linked to AD neuropathology through unknown mechanisms.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Rebecca Panitch et al.
Summary: The study found that the protective effect of APOE ε2 against Alzheimer's disease may be related to the complement pathway, involving genes such as C4A, C4B, and HSPA2. An AD-specific co-expression network was identified in APOE ε2/ε3 carriers, primarily associated with tau pathology.
MOLECULAR PSYCHIATRY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Zhangying Chen et al.
Summary: The three-dimensional graphic design illustrates the potential role of meningeal vessels in Alzheimer disease, showing the clearance of solutes from meningeal lymphatic vessels. The image highlights differences between APOE4(+) and APOE4(-) Alzheimer disease cases outlined in the accompanying Comment article.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Luis Enrique Arroyo-Garcia et al.
Summary: The study found a significant degradation in gamma oscillation power in the App(NL-G-F) mouse model, independent of and preceding amyloid plaque formation and cognitive impairment reported previously. This degradation is correlated with increased concentration of A beta(1-42) in the brain.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Ya-Nan Ou et al.
Summary: The study identified 7 brain proteins as causal in Alzheimer's disease, with ACE and SNX32 also being associated with AD at the blood transcriptomic level. These findings may provide important leads for future functional studies and potential drug targets for AD.
MOLECULAR PSYCHIATRY
(2021)
Correction
Biochemistry & Molecular Biology
Zhangying Chen et al.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Sujeong Yang et al.
Summary: Perineuronal nets (PNNs), containing chondroitin sulphate proteoglycans on neuronal surfaces, play a role in neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) in PNNs leads to increased inhibition. Manipulating CS composition of PNNs can restore neuroplasticity and memory deficits in aged mice, with a focus on the importance of C6S in memory and neuroplasticity.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Valeria Calsolaro et al.
Summary: This study utilized a novel PET tracer, C-11-BU99008, to investigate astrocyte reactivity associated with Alzheimer's disease, revealing significantly increased astrocyte reactivity in older cognitively impaired and Alzheimer's disease patients, particularly in cortical regions.
MOLECULAR PSYCHIATRY
(2021)
Correction
Biochemistry & Molecular Biology
Ivan Alic et al.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Mary Ann A. DeMichele-Sweet et al.
Summary: Psychotic symptoms in Alzheimer's disease are common and have genetic components, with significant associations found in two loci - ENPP6 and SUMF1. AD + P shows negative genetic correlations with cognitive and educational attainment, and positive genetic correlations with depressive symptoms. This study provides insights into the genetic architecture of psychosis in Alzheimer's disease.
MOLECULAR PSYCHIATRY
(2021)
Review
Biochemistry & Molecular Biology
Harald Hampel et al.
Summary: Breakthroughs in molecular medicine have highlighted the significance of the amyloid-beta pathway in the pathophysiology of Alzheimer's disease. Established biochemical alterations of the A beta cycle serve as promising targets for the development of disease-modifying therapies. Research indicates a crucial role of A beta pathway dyshomeostasis in the dynamics of AD pathophysiology, supporting the development of A beta-targeting therapeutic strategies for early treatment of AD.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Fanny Eysert et al.
Summary: Research has shown that FERMT2 plays an important regulatory role in APP metabolism, and underexpression of FERMT2 can affect axonal growth, synaptic connectivity, and long-term potentiation, which may impact the pathogenesis of Alzheimer's disease (AD).
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
J. I. Velez et al.
MOLECULAR PSYCHIATRY
(2016)