Dataset Information
RBFOX1 association with age at onset of Alzheimer's disease.
Ontology highlight
ABSTRACT: Introduction
Genetic contributors to early onset Alzheimer's disease (AD) beyond APP and PSEN1/2 remain unknown. Identifying novel loci may reveal disease mechanisms and therapeutic targets. We investigated genetic variants influencing age at onset in early onset families from the Long-Life Family Study (LLFS).Methods
Six families with at least two early onset cases (onset ≤ 65) were identified among 3476 LLFS participants. Genome-wide linkage analysis of age at onset was followed by single nucleotide polymorphism association. Validation analyses were performed in nine independent cohorts, alongside blood and brain transcriptomic analyses.Results
Three significant linkage regions were identified, including RBFOX1 (logarithm of the odds = 4.41). RBFOX1 variants were associated with age at onset and cognitive phenotypes. A consistent association of RBFOX1 was observed across validation cohorts. Blood transcriptomics revealed RBFOX1 overexpression was associated with an earlier onset.Discussion
RBFOX1 may influence AD age of onset, nominating the gene as a potential therapeutic target for delaying or preventing dementia.
SUBMITTER: Xicota L
PROVIDER: S-EPMC12928012 | biostudies-literature | 2026 Feb
REPOSITORIES: biostudies-literature
Publications
RBFOX1 association with age at onset of Alzheimer's disease.
Alzheimer's & dementia : the journal of the Alzheimer's Association 20260201 2
<h4>Introduction</h4>Genetic contributors to early onset Alzheimer's disease (AD) beyond APP and PSEN1/2 remain unknown. Identifying novel loci may reveal disease mechanisms and therapeutic targets. We investigated genetic variants influencing age at onset in early onset families from the Long-Life Family Study (LLFS).<h4>Methods</h4>Six families with at least two early onset cases (onset ≤ 65) were identified among 3476 LLFS participants. Genome-wide linkage analysis of age at onset was followe ...[more]
