Polygenic risk scores for Alzheimer's disease are related to dementia risk in APOE ɛ4 negatives

Alzheimers Dement (Amst). 2021 Jan 22;13(1):e12142. doi: 10.1002/dad2.12142. eCollection 2021.


Introduction: Studies examining the effect of polygenic risk scores (PRS) for Alzheimer's disease (AD) and apolipoprotein E (APOE) genotype on incident dementia in very old individuals are lacking.

Methods: A population-based sample of 2052 individuals ages 70 to 111, from Sweden, was followed in relation to dementia. AD-PRSs including 39, 57, 1333, and 13,942 single nucleotide polymorphisms (SNPs) were used.

Results: AD-PRSs (including 39 or 57 SNPs) were associated with dementia (57-SNPs AD-PRS: hazard ratio 1.09, confidence interval 1.01-1.19, P = .03), particularly in APOE ɛ4 non-carriers (57-SNPs AD-PRS: 1.15, 1.05-1.27, P = 4 × 10-3, 39-SNPs AD-PRS: 1.22, 1.10-1.35, P = 2 × 10-4). No association was found with the other AD-PRSs. Further, APOE ɛ4 was associated with increased risk of dementia (1.60, 1.35-1.92, P = 1 × 10-7). In those aged ≥95 years, the results were similar for the AD-PRSs, while APOE ɛ4 only predicted dementia in the low-risk tertile of AD-PRSs.

Discussion: These results provide information to identify individuals at increased risk of dementia.

Keywords: Alzheimer's disease; apolipoprotein E genotype; dementia; polygenic risk score; risk factors in epidemiology.