Open AccessAssociations between rare microglia‐linked Alzheimer's disease risk variants and subcortical brain volumes in young individuals
Author(s) -
Lancaster Thomas M.
Publication year - 2019
Publication title -
alzheimer's and dementia: diagnosis, assessment and disease monitoring
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.497
H-Index - 37
ISSN - 2352-8729
DOI - 10.1016/j.dadm.2019.03.005
Subject(s) - trem2 , microglia , putamen , basal ganglia , disease , neuroscience , exome sequencing , biology , early onset alzheimer's disease , alzheimer's disease , medicine , genetics , mutation , central nervous system , pathology , gene , inflammation
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.