Aducanumab-Hope or Disappointment for Alzheimer's Disease

Article Biochemistry & Molecular Biology

Senile plaques in Alzheimer's disease arise from Aβ- and Cathepsin D-enriched mixtures leaking out during intravascular haemolysis and microaneurysm rupture

Hualin Fu et al.

Summary: This study reveals that the formation of senile plaques is associated with the leakage of substances enriched with Aβ and Cathepsin D through blood.

FEBS LETTERS (2023)

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Article Clinical Neurology

Aducanumab Use in Symptomatic Alzheimer Disease Evidence in Focus A Report of the AAN Guidelines Subcommittee

Gregory S. Day et al.

Summary: This study systematically reviewed clinical trial data and classified the evidence level for the use of aducanumab in Alzheimer's disease treatment. It found that aducanumab was safe and well tolerated in certain doses, and it decreased amyloid deposition in the brain. However, its clinical efficacy is still uncertain. The use of aducanumab would require expanded clinical infrastructure, and evidence-based guidelines are needed to address key questions.

NEUROLOGY (2022)

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Article Clinical Neurology

Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer Disease

Stephen Salloway et al.

Summary: The EMERGE and ENGAGE phase 3 trials provided data on ARIA associated with aducanumab treatment in patients with Alzheimer's disease. A high rate of ARIA was observed, with ARIA-edema being the most common adverse event. Some patients in the aducanumab group experienced associated symptoms, with headache being the most common.

JAMA NEUROLOGY (2022)

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Article Cell Biology

Early Cellular, Molecular, Morphological and Behavioral Changes in the Humanized Amyloid-Beta-Knock-In Mouse Model of Late-Onset Alzheimer's Disease

Sudhir Kshirsagar et al.

Summary: The purpose of this study is to investigate the early cellular, molecular, morphological, and behavioral changes in humanized amyloid-beta-knock-in (hAbKI) mice. The findings suggest that amyloid-beta is sufficient to cause behavioral, mitochondrial, synaptic, and ultrastructural changes in mice.

CELLS (2022)

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Editorial Material Clinical Neurology

Practical Considerations in the Administration of Aducanumab for the Neurologist

Katherine Coerver et al.

Summary: Aducanumab (Aduhelm), developed by Biogen, has been approved by the FDA through an accelerated approval pathway. Initially approved for all forms of Alzheimer's disease, its label was later updated to specify treatment for patients with mild cognitive impairment or mild dementia. This approval has garnered national interest due to the large number of AD patients in the US.

NEUROLOGY-CLINICAL PRACTICE (2022)

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Review Medicine, Research & Experimental

Aducanumab making a comeback in Alzheimer's disease: An old wine in a new bottle

Tapan Behl et al.

Summary: The article discusses the discovery of aducanumab as an antibody-based immunotherapy for Alzheimer's disease and the controversies surrounding its FDA approval. It explores the failure of anti-amyloid therapies in AD and the impact of aducanumab in AD models, as well as its potential implications.

BIOMEDICINE & PHARMACOTHERAPY (2022)

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Review Pharmacology & Pharmacy

Blood-brain barrier leakage in Alzheimer's disease: From discovery to clinical relevance

Geetika Nehra et al.

Summary: This review summarizes the extent and clinical relevance of barrier leakage in Alzheimer's disease (AD). By examining animal models, clinical and postmortem studies, signaling mechanisms, and potential therapeutic strategies, the review provides insights into the relationship between barrier leakage and neurodegeneration, cognitive decline, and the development of novel therapeutic targets for AD.

PHARMACOLOGY & THERAPEUTICS (2022)

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Review Pharmacology & Pharmacy

Therapeutic Approach to Alzheimer's Disease: Current Treatments and New Perspectives

Teresa Pardo-Moreno et al.

Summary: This article discusses the treatment approaches for Alzheimer's disease, including approved drugs, investigational therapies, and alternative methods to improve lifestyle.

PHARMACEUTICS (2022)

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Review Pharmacology & Pharmacy

Therapeutic nanotechnologies for Alzheimer's disease: A critical analysis of recent trends and findings

Philippe Delbreil et al.

Summary: Nanotechnology holds great promise in the treatment of Alzheimer's Disease, but faces numerous challenges including effective drug delivery and commercialization barriers.

ADVANCED DRUG DELIVERY REVIEWS (2022)

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Review Cell Biology

Comparative efficacy of lithium and aducanumab for cognitive decline in patients with mild cognitive impairment or Alzheimer?s disease: A systematic review and network meta-analysis

Itsuki Terao et al.

Summary: The research indicated that lithium was significantly more effective than aducanumab in treating cognitive decline in patients with MCI and AD.

AGEING RESEARCH REVIEWS (2022)

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Review Clinical Neurology

Shared pathophysiology: Understanding stroke and Alzheimer's disease

Sai Sriram et al.

Summary: This critical review examines the shared vascular risk factors between Alzheimer's disease and stroke, as well as their pathophysiology and interplay. The review highlights areas that require further investigation and discusses the potential of targeting secondary mechanisms early in treatment options.

CLINICAL NEUROLOGY AND NEUROSURGERY (2022)

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Article Chemistry, Medicinal

New Aβ(1-42) ligands from anti-amyloid antibodies: Design, synthesis, and structural interaction

Angelo Santoro et al.

Summary: Alzheimer's disease is a common neurodegenerative disorder characterized by the accumulation of amyloid plaques. Many molecules targeting A beta peptides and anti-A beta monoclonal antibodies have been screened as potential drug candidates. In this study, short peptide sequences were designed based on the binding sites of A beta(1-42)/antibodies, and two peptides, WAibH and SYSTPGK, were identified as mimics of solanezumab and aducanumab, respectively. These antibody-derived peptides were found to interact with soluble A beta(1-42) and control its aggregation.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2022)

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Review Clinical Neurology

A tough trek in the development of an anti-amyloid therapy for Alzheimer's disease: Do we see hope in the distance?

Jin Jun Luo et al.

Summary: The search for effective therapy for Alzheimer's disease patients has been challenging, with the recent approval of Aducanumab sparking controversy due to questions surrounding its appropriateness. Various hypotheses including amyloid and tau protein aggregation remain controversial, but Aducanumab did show some benefit in mild AD patients. Understanding these hypotheses and controversies is important to evaluate the limitations and challenges in treating AD patients and exploring more efficacious therapies in the future.

JOURNAL OF THE NEUROLOGICAL SCIENCES (2022)

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Review Neurosciences

Based on molecular structures: Amyloid-β generation, clearance, toxicity and therapeutic strategies

Hai Yang et al.

Summary: This review discusses the metabolism and toxicity of Aβ, as well as the therapeutic strategies for AD based on the latest progress in its molecular structures. The development of structural biology technology has provided new insights into the role of Aβ in AD.

FRONTIERS IN MOLECULAR NEUROSCIENCE (2022)

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Review Psychology, Clinical

Aducanumab, a Novel Anti-Amyloid Monoclonal Antibody, for the Treatment of Alzheimer's Disease: A Comprehensive Review

Hannah W. Haddad et al.

Summary: Alzheimer's disease is a common form of dementia with significant impact on patients and caregivers. Aducanumab, the only FDA-approved drug to slow disease progression, shows promise in restoring neurological function by reducing amyloid plaques. However, its clinical significance is still under debate.

HEALTH PSYCHOLOGY RESEARCH (2022)

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Article Biochemistry & Molecular Biology

Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media

Hind Al Khashali et al.

Summary: Comparing two human lung cancer cells, we found different levels of AChE, A beta, and mBDNF in the media of H1299 and A549 cells. We hypothesized that sAPP alpha levels are regulated by AChE and mBDNF. Knockdown of AChE increased sAPP alpha levels and decreased intact A beta 40/42 levels in A549 cell media. AChE and mBDNF had opposite effects on A beta and sAPP alpha levels and operated through alpha-secretase activity.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Clinical Neurology

Role of Calcium Homeostasis in Alzheimer's Disease

Mengqian Ge et al.

Summary: Alzheimer's disease is a neurodegenerative disease characterized by senile plaques and neurofibrillary tangles in the brain. The dysregulation of intracellular calcium homeostasis has been implicated in the pathogenesis of the disease and shows potential as a therapeutic target.

NEUROPSYCHIATRIC DISEASE AND TREATMENT (2022)

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Review Cell Biology

Past, present and future of therapeutic strategies against amyloid-β peptides in Alzheimer's disease: a systematic review

Danko Jeremic et al.

Summary: Alzheimer's disease is the most common neurodegenerative disease in aging population with lack of effective treatments. Accumulation of Aβ peptides is considered one of the fundamental neuropathological pillars of the disease, thus many therapies target Aβ.

AGEING RESEARCH REVIEWS (2021)

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Article Clinical Neurology

A multifactorial model of pathology for age of onset heterogeneity in familial Alzheimer's disease

Diego Sepulveda-Falla et al.

Summary: PSEN1-E280A carriers exhibit a bimodal distribution of disease onset age, with no clinical differences between different age groups. Although mutant PSEN1 affects the production of Aβ, there are no significant differences in the generation and deposition of Aβ between groups. However, early-onset patients show severe hyperphosphorylated Tau pathology, while late-onset patients exhibit lesser pTau pathology and a distinct kinase activity.

ACTA NEUROPATHOLOGICA (2021)

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Review Chemistry, Medicinal

Monoclonal Antibodies as Neurological Therapeutics

Panagiotis Gklinos et al.

Summary: Monoclonal antibodies play a crucial role in therapy and have revolutionized treatment in neurology. Ongoing research is exploring the potential of more monoclonal antibodies for treating neurological diseases, with a focus on understanding disease mechanisms for more precise targeted therapy.

PHARMACEUTICALS (2021)

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Editorial Material Neurosciences

Aducanumab and the post-amyloid'' era of Alzheimer research?

Erik S. Musiek et al.

NEURON (2021)

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Article Neurosciences

Amyloid-Beta Mediates Homeostatic Synaptic Plasticity

Christos Galanis et al.

Summary: Recent studies have shown that APP plays a crucial physiological role in synaptic plasticity, especially in homeostatic synaptic plasticity. Processing of APP through the amyloidogenic pathway may be important for maintaining brain homeostasis and brain states associated with increased amyloid-b levels.

JOURNAL OF NEUROSCIENCE (2021)

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Article Biochemistry & Molecular Biology

Current Understanding of the Physiopathology, Diagnosis and Therapeutic Approach to Alzheimer's Disease

Victoria Garcia-Morales et al.

Summary: Alzheimer's disease is characterized by cognitive decline and memory loss, with the amyloid cascade hypothesis being the leading theory in its pathophysiology. Diagnosis is currently based on clinical parameters and fluid-based biomarkers, with treatment focusing on symptom control through pharmacological and nonpharmacological approaches. Further research is needed to identify new biomarkers and therapies to prevent progression of the disease.

BIOMEDICINES (2021)

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Review Neurosciences

Protective genes and pathways in Alzheimer's disease: moving towards precision interventions

Mabel Seto et al.

Summary: Alzheimer's disease is a complex neurodegenerative disorder with both genetic and environmental factors contributing to its etiology. Recent focus has shifted towards individuals who show resistance or resilience to the pathology of the disease, offering potential insights into new biological mechanisms and therapeutic targets. This review highlights some genes and variants that provide protection from AD and suggests avenues for developing precision interventions leveraging the ideas of protection and resilience.

MOLECULAR NEURODEGENERATION (2021)

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Editorial Material Medicine, General & Internal

The Problem of Aducanumab for the Treatment of Alzheimer Disease

G. Caleb Alexander et al.

ANNALS OF INTERNAL MEDICINE (2021)

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Review Biochemistry & Molecular Biology

Elevating the Levels of Calcium Ions Exacerbate Alzheimer's Disease via Inducing the Production and Aggregation of β-Amyloid Protein and Phosphorylated Tau

Pei-Pei Guan et al.

Summary: This review summarizes the mechanisms by which Ca2+ affects the development and progression of AD, including the transport of Ca2+ into and out of cells and organelles, the influence of Ca2+ imbalance on Aβ peptides and tau protein, and the impact on learning and memory. The molecular network through which Ca2+ regulates the pathogenesis of AD is also presented.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Biochemistry & Molecular Biology

An Unbalanced Synaptic Transmission: Cause or Consequence of the Amyloid Oligomers Neurotoxicity?

Miriam Sciaccaluga et al.

Summary: Oligomeric A beta proteins exert toxicity through interaction with membrane receptors and formation of ion-permeable channels, affecting synaptic function and network structure.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Neurosciences

Extracellular protein components of amyloid plaques and their roles in Alzheimer's disease pathology

M. Mahafuzur Rahman et al.

Summary: Alzheimer's disease is pathologically defined by the presence of A beta in extracellular senile plaques and tau in intracellular neurofibrillary tangles. Besides A beta, other constituents are accumulated in the plaques, mainly focusing on extracellular proteins, which may contribute to disruptions in the protein network and lead to AD and copathology. This review provides an overview of extracellular proteins interacting with A beta and their potential roles in AD pathology, as well as methods to analyze the incorporation of proteins in plaques.

MOLECULAR NEURODEGENERATION (2021)

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Review Biochemistry & Molecular Biology

Role of Monoamine Oxidase Activity in Alzheimer's Disease: An Insight into the Therapeutic Potential of Inhibitors

Tapan Behl et al.

Summary: Despite being less utilized in depression treatment compared to other antidepressants, monoamine oxidase inhibitors (MAOIs) have shown potential in neuroprotection and treatment of neurological and psychiatric conditions. Research on MAOIs, particularly on their neuroprotective activities, has been progressing, indicating a possible role in conditions like Alzheimer's disease. The therapeutic potential of MAOIs, especially in neurodegenerative diseases, suggests a promising future for these drugs with a better understanding of their physiology.

MOLECULES (2021)

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Article Biochemistry & Molecular Biology

Kinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies

Sara Linse et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2020)

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Review Pharmacology & Pharmacy

Alzheimer's disease: Recent treatment strategies

Miguel Vaz et al.

EUROPEAN JOURNAL OF PHARMACOLOGY (2020)

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Review Cell Biology

Development of therapeutic antibodies for the treatment of diseases

Ruei-Min Lu et al.

JOURNAL OF BIOMEDICAL SCIENCE (2020)

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Review Medicine, Research & Experimental

An attempt to elucidate the role of iron and zinc ions in development of Alzheimer's and Parkinson's diseases

Karolina Wojtunik-Kulesza et al.

BIOMEDICINE & PHARMACOTHERAPY (2019)

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Article Biochemistry & Molecular Biology

In vivo localization of human acetylcholinesterase-derived species in a -sheet conformation at the core of senile plaques in Alzheimer's disease

Letitia Jean et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2019)

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Article Medicine, General & Internal

Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia

Gil D. Rabinovici et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2019)

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Editorial Material Clinical Neurology

Alzheimer disease and aducanumab: adjusting our approach

Dennis J. Selkoe

NATURE REVIEWS NEUROLOGY (2019)

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Review Neurosciences

Anti-Amyloid-β Monoclonal Antibodies for Alzheimer's Disease: Pitfalls and Promise

Christopher H. van Dyck

BIOLOGICAL PSYCHIATRY (2018)

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Review Biochemistry & Molecular Biology

Peptides as Potential Therapeutics for Alzheimer's Disease

Samo Ribaric

MOLECULES (2018)

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Article Neurosciences

Imbalance between firing homeostasis and synaptic plasticity drives early-phase Alzheimer's disease

Boaz Styr et al.

NATURE NEUROSCIENCE (2018)

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Review Clinical Neurology

Review of the advances in treatment for Alzheimer disease: Strategies for combating beta-amyloid protein

J. Folch et al.

NEUROLOGIA (2018)

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Article Multidisciplinary Sciences

Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β

Joseph W. Arndt et al.

SCIENTIFIC REPORTS (2018)

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Review Health Care Sciences & Services

Precision Medicine for Alzheimer's Disease Prevention

Cara L. Berkowitz et al.

HEALTHCARE (2018)

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Article Gerontology

A life-course and multifactorial approach to Alzheimer's disease: Implications for research, clinical assessment and intervention practices

Martial Van der Linden et al.

DEMENTIA-INTERNATIONAL JOURNAL OF SOCIAL RESEARCH AND PRACTICE (2018)

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Article Clinical Neurology

A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease

Susanne Ostrowitzki et al.

ALZHEIMERS RESEARCH & THERAPY (2017)

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Article Neurosciences

Immunotherapy with Aducanumab Restores Calcium Homeostasis in Tg2576 Mice

Ksenia V. Kastanenka et al.

JOURNAL OF NEUROSCIENCE (2016)

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Article Multidisciplinary Sciences

The antibody aducanumab reduces Aβ plaques in Alzheimer's disease

Jeff Sevigny et al.

NATURE (2016)

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Article Clinical Neurology

Safety and tolerability of BAN2401-a clinical study in Alzheimer's disease with a protofibril selective Aβ antibody

Veronika Logovinsky et al.

ALZHEIMERS RESEARCH & THERAPY (2016)

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Review Medicine, General & Internal

The Role of Amyloid-β Oligomers in Toxicity, Propagation, and Immunotherapy

Urmi Sengupta et al.

EBIOMEDICINE (2016)

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Review Biochemistry & Molecular Biology

Oxidative stress and mitochondrial dysfunction in Alzheimer's disease

Xinglong Wang et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE (2014)

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Review Cell Biology

Calcium dysregulation and neuroinflammation: Discrete and integrated mechanisms for age-related synaptic dysfunction

Diana M. Sama et al.

AGEING RESEARCH REVIEWS (2013)

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Article Clinical Neurology

Amyloid-Beta Oligomerization in Alzheimer Dementia versus High-Pathology Controls

Thomas J. Esparza et al.

ANNALS OF NEUROLOGY (2013)

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Review Neurosciences

Immunotherapy for Alzheimer's disease: hoops and hurdles

Cynthia A. Lemere

MOLECULAR NEURODEGENERATION (2013)

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Article Multidisciplinary Sciences

Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment

Gwenaelle Douaud et al.

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

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Article Multidisciplinary Sciences

Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism

Samuel I. A. Cohen et al.

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

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Article Neurosciences

The systemic iron-regulatory proteins hepcidin and ferroportin are reduced in the brain in Alzheimer's disease

Animesh Alexander Raha et al.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2013)

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Article Pharmacology & Pharmacy

Monoclonal antibody therapeutics: history and future

Nicholas A. P. S. Buss et al.

CURRENT OPINION IN PHARMACOLOGY (2012)

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Review Clinical Neurology

Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature

Peter T. Nelson et al.

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY (2012)

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Article Neurosciences

A Plaque-Specific Antibody Clears Existing β-amyloid Plaques in Alzheimer's Disease Mice

Ronald B. DeMattos et al.

NEURON (2012)

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Article Medicine, Research & Experimental

The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment

Rawan Tarawneh et al.

COLD SPRING HARBOR PERSPECTIVES IN MEDICINE (2012)

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Review Clinical Neurology

Brain microbleeds and Alzheimer's disease: innocent observation or key player?

Charlotte Cordonnier et al.

BRAIN (2011)

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Article Biochemistry & Molecular Biology

Transformation of amyloid β(1-40) oligomers into fibrils is characterized by a major change in secondary structure

Rabia Sarroukh et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2011)

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Alzheimer's disease

Clive Ballard et al.

LANCET (2011)

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Article Clinical Neurology

Alzheimer's disease, a multifactorial disorder seeking multitherapies

Khalid Iqbal et al.

ALZHEIMERS & DEMENTIA (2010)

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Article Clinical Neurology

Spatial Relation Between Microbleeds and Amyloid Deposits in Amyloid Angiopathy

Gregory A. Dierksen et al.

ANNALS OF NEUROLOGY (2010)

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Article Medicine, General & Internal

Long-term effects of Aβ42 immunisation in Alzheimer's disease:: follow-up of a randomised, placebo-controlled phase I trial

Clive Holmes et al.

LANCET (2008)

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Article Clinical Neurology

Changes in readthrough acetylcholinesterase expression modulate amyloid-beta pathology

Amit Berson et al.

BRAIN (2008)

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Article Biochemistry & Molecular Biology

Distinct early folding and aggregation properties of Alzheimer amyloid-β peptides Aβ40 and Aβ42 -: Stable trimer or tetramer formation by Aβ42

Yun-Ru Chen et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2006)

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Article Endocrinology & Metabolism

Pericapillary haem-rich deposits:: evidence for microhaemorrhages in aging human cerebral cortex

KM Cullen et al.

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM (2005)

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Article Neurosciences

Aβ immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasome

S Oddo et al.

NEURON (2004)

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Article Clinical Neurology

Deposits of fibrillar Aβ do not cause neuronal loss or ferritin expression in adult rat brain

GM Bishop et al.

JOURNAL OF NEURAL TRANSMISSION (2003)

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Article Pathology

Age-related amyloid β deposition in transgenic mice overexpressing both Alzheimer mutant presenilin 1 and amyloid β precursor protein Swedish mutant is not associated with global neuronal loss

A Takeuchi et al.

AMERICAN JOURNAL OF PATHOLOGY (2000)

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Aducanumab-Hope or Disappointment for Alzheimer's Disease

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