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Article
Clinical Meaningfulness in Alzheimer’s Disease Clinical Trials. A Report from the EU-US CTAD Task Force
Recent positive results of three phase III anti-amyloid monoclonal antibody trials are transforming the landscape of disease-modifying therapeutics for Alzheimer’s disease, following several decades of failure...
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Article
Open AccessAmyloid-beta antibody binding to cerebral amyloid angiopathy fibrils and risk for amyloid-related imaging abnormalities
Therapeutic antibodies have been developed to target amyloid-beta (Aβ), and some of these slow the progression of Alzheimer’s disease (AD). However, they can also cause adverse events known as amyloid-related ...
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Article
Open AccessAltered amyloid-β structure markedly reduces gliosis in the brain of mice harboring the Uppsala APP deletion
Deposition of amyloid beta (Aβ) into plaques is a major hallmark of Alzheimer’s disease (AD). Different amyloid precursor protein (APP) mutations cause early-onset AD by altering the production or aggregation pro...
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Article
Neuropsychiatric Symptoms in AD: Clinical Trials Targeting Mild Behavioral Impairment: A Report from the International CTAD Task Force
The International CTAD Task Force (TF) addressed challenges related to designing clinical trials for agitation in dementia, presenting accomplishments from the two previous TFs on neuropsychiatric symptoms (NP...
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Article
Can We Use Blood Biomarkers as Entry Criteria and for Monitoring Drug Treatment Effects in Clinical Trials? A Report from the EU/US CTAD Task Force
In randomized clinical trials (RCTs) for Alzheimer’s Disease (AD), cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers are currently used for the detection and monitoring of AD patholog...
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Article
Open AccessThe interwoven fibril-like structure of amyloid-beta plaques in mouse brain tissue visualized using super-resolution STED microscopy
Standard neuropathologic analysis of Alzheimer’s brain relies on traditional fluorescence microscopy, which suffers from limited spatial resolution due to light diffraction. As a result, it fails to reveal int...
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Article
Open AccessLecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease
Immunotherapy against amyloid-beta (Aβ) is a promising option for the treatment of Alzheimer’s disease (AD). Aβ exists as various species, including monomers, oligomers, protofibrils, and insoluble fibrils in ...
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Article
Open AccessCorrection: A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody
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Article
Open AccessMutation analysis of disease causing genes in patients with early onset or familial forms of Alzheimer’s disease and frontotemporal dementia
Most dementia disorders have a clear genetic background and a number of disease genes have been identified. Mutations in the tau gene (MAPT) lead to frontotemporal dementia (FTD), whereas mutations in the genes f...
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Article
Open AccessThe Amyloid-β Pathway in Alzheimer’s Disease
Breakthroughs in molecular medicine have positioned the amyloid-β (Aβ) pathway at the center of Alzheimer’s disease (AD) pathophysiology. While the detailed molecular mechanisms of the pathway and the spatial-...
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Article
Open AccessNovel multivalent design of a monoclonal antibody improves binding strength to soluble aggregates of amyloid beta
Amyloid-β (Aβ) immunotherapy is a promising therapeutic strategy in the fight against Alzheimer’s disease (AD). A number of monoclonal antibodies have entered clinical trials for AD. Some of them have failed d...
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Article
Open AccessHeparanase overexpression impedes perivascular clearance of amyloid-β from murine brain: relevance to Alzheimer’s disease
Defective amyloid-β (Aβ) clearance from the brain is a major contributing factor to the pathophysiology of Alzheimer’s disease (AD). Aβ clearance is mediated by macrophages, enzymatic degradation, perivascular...
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Article
Publisher Correction: Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
A Correction to this paper has been published: https://doi.org/10.1038/s41588-021-00832-z.
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Article
Open AccessA randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody
Lecanemab (BAN2401), an IgG1 monoclonal antibody, preferentially targets soluble aggregated amyloid beta (Aβ), with activity across oligomers, protofibrils, and insoluble fibrils. BAN2401-G000-201, a randomize...
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Article
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated g...
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Article
Author Correction: Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Article
Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
Risk for late-onset Alzheimer’s disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinicall...
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Article
Mosaic loss of chromosome Y in leukocytes matters
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Open AccessAlzheimer’s disease pathology propagation by exosomes containing toxic amyloid-beta oligomers
The gradual deterioration of cognitive functions in Alzheimer’s disease is paralleled by a hierarchical progression of amyloid-beta and tau brain pathology. Recent findings indicate that toxic oligomers of amy...
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Article
Open AccessEfficient clearance of Aβ protofibrils in AβPP-transgenic mice treated with a brain-penetrating bifunctional antibody
Amyloid-β (Aβ) immunotherapy is one of the most promising disease-modifying strategies for Alzheimer’s disease (AD). Despite recent progress targeting aggregated forms of Aβ, low antibody brain penetrance rema...
