Alzheimer's & dementia : the journal of the Alzheimer's Association
Pathway-specific polygenic risk scores modify the association between amyloid and tau PET accumulation in patients with Alzheimer's disease
By Valentim C, Denecke J, Frerich S and 7 others.
Abstract
Background
Genome-wide association studies (GWASs) identified multiple genetic variants associated with Alzheimer's disease (AD) risk, yet the biological pathways linking these to amyloid and tau pathology remain unclear.
Methods
We conducted a meta-analysis of recent GWASs to identify independent genome-wide significant single nucleotide polymorphisms which were mapped via gene-set enrichment to derive pathway-specific polygenic risk scores (pPRSs). Analyses included 441 amyloid-positive participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI; 224 with longitudinal tau positron emission tomography [PET]) and 250 amyloid-positive participants from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study (113 with longitudinal tau PET). Robust linear regressions tested cross-sectional and longitudinal pPRS-by-amyloid chronicity interactions on tau PET.