Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

APOE ε4's impact on response to amyloid therapies in early symptomatic Alzheimer's disease: Analyses from multiple clinical trials

APOE ε4's impact on response to amyloid therapies in early symptomatic Alzheimer's disease:... BACKGROUNDIn Alzheimer's disease (AD), accumulation and aggregation of amyloid beta (Aβ) peptide into extracellular amyloid plaques is an early event that precedes neurodegeneration and cognitive and functional impairment.1–3 Genetic variants are also shown to be involved in the onset of AD.4,5 This is the case for the apolipoprotein E (APOE) gene on chromosome 19, because having the APOE ε4 allele increases the risk of developing AD6 and is associated with amyloid accumulation and an earlier age of disease onset.4,7 Based on the hypothesis that early pathogenesis of AD might be due to overproduction of amyloid plaques or to a decreased clearance rate, there has been focus on the use of amyloid‐targeting antibody drugs in AD clinical trials.8The role of apoE4 in amyloid accumulation has been described,9 and the risk for AD increases in a gene–dose‐dependent manner.10 While APOE ε4 as a risk factor is well established, the role of apoE4 in progression after controlling for the presence of amyloid is more uncertain. Conflicting studies suggest that the APOE ε4 allele has no effect on disease progression even without accounting for the presence or absence of amyloid pathology.11,12 Currently, trials on amyloid‐targeting drugs, particularly antibody‐based therapies, generally enroll only amyloid‐positive http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Alzheimer s & Dementia Wiley

APOE ε4's impact on response to amyloid therapies in early symptomatic Alzheimer's disease: Analyses from multiple clinical trials

Download PDF
11 pages

Loading next page...
 
/lp/wiley/apoe-4-s-impact-on-response-to-amyloid-therapies-in-early-symptomatic-4G0i3RPYHh

References (35)

Publisher
Wiley
Copyright
© 2023 the Alzheimer's Association.
ISSN
1552-5260
eISSN
1552-5279
DOI
10.1002/alz.13128
Publisher site
See Article on Publisher Site

Abstract

BACKGROUNDIn Alzheimer's disease (AD), accumulation and aggregation of amyloid beta (Aβ) peptide into extracellular amyloid plaques is an early event that precedes neurodegeneration and cognitive and functional impairment.1–3 Genetic variants are also shown to be involved in the onset of AD.4,5 This is the case for the apolipoprotein E (APOE) gene on chromosome 19, because having the APOE ε4 allele increases the risk of developing AD6 and is associated with amyloid accumulation and an earlier age of disease onset.4,7 Based on the hypothesis that early pathogenesis of AD might be due to overproduction of amyloid plaques or to a decreased clearance rate, there has been focus on the use of amyloid‐targeting antibody drugs in AD clinical trials.8The role of apoE4 in amyloid accumulation has been described,9 and the risk for AD increases in a gene–dose‐dependent manner.10 While APOE ε4 as a risk factor is well established, the role of apoE4 in progression after controlling for the presence of amyloid is more uncertain. Conflicting studies suggest that the APOE ε4 allele has no effect on disease progression even without accounting for the presence or absence of amyloid pathology.11,12 Currently, trials on amyloid‐targeting drugs, particularly antibody‐based therapies, generally enroll only amyloid‐positive

Journal

Alzheimer s & Dementia – Wiley

Published: Dec 1, 2023

Keywords: Alzheimer's disease; amyloid plaque; amyloid‐targeting therapy; apolipoprotein E ( APOE ); cognition; disease progression; efficacy

There are no references for this article.