Associations between rare microglia-linked Alzheimer's disease risk variants and subcortical brain volumes in young individuals.

ABSTRACT: Introduction:Recent exome sequencing studies have identified three novel risk variants associated with Alzheimer's disease (AD). However, the mechanisms by which these variants confer risk are largely unknown. Methods:In the present study, the impact of these rare coding variants (in ABI3, PLCG2, and TREM2) on all subcortical volumes is determined in a large sample of young healthy individuals (N = 756-765; aged 22-35 years). Results:After multiple testing correction (P CORRECTED < .05), rare variants were associated with basal ganglia volumes (TREM2 and PLCG2 effects within the putamen and pallidum, respectively). Nominal associations between TREM2 and reduced hippocampal and thalamic volumes were also observed. Discussion:Our observations suggest that rare variants in microglia-mediated immunity pathway may contribute to the subcortical alterations observed in AD cases. These observations provide further evidence that genetic risk for AD may influence the volume of subcortical volumes and increase AD risk in early life processes.

SUBMITTER: Lancaster TM 

PROVIDER: S-EPMC6501059 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature