<i>APOE</i> stratified genome-wide association studies provide novel insights into the genetic etiology of Alzheimers's disease.

ABSTRACT: Among the more than 90 identified genetic risk loci for late-onset Alzheimer's disease (AD) and related dementias, the apolipoprotein E gene (APOE) ε2/ε3/ε4 polymorphism remains the longstanding benchmark for genetic disease risk with a consistently large effect across studies^1-10. Despite this massive signal, the exact mechanisms for how ε4 increases and for how ε2 decreases dementia risk is not well-understood. Importantly, recent trials of anti-amyloid therapies suggest less efficacy and higher risks of severe side effects in s4 carriers^11-13, hampering the treatment of those with the highest unmet need. To improve our understanding of the genetic architecture of AD in the context of its main genetic driver, we performed genome-wide association studies (GWAS

SUBMITTER: Thomassen JQ 

PROVIDER: S-EPMC12083631 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature