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TOMM40 intron 6 poly‐T length, age at onset, and neuropathology of AD in individuals with APOE ɛ3/ɛ3
Author(s) -
Li Ge,
Bekris Lynn M.,
Leong Lesley,
Steinbart Ellen J.,
Shofer Jane B.,
Crane Paul K.,
Larson Eric B.,
Peskind Elaine R.,
Bird Thomas D.,
Yu ChangEn
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.06.009
Subject(s) - neuropathology , psen1 , presenilin , apolipoprotein e , senile plaques , age of onset , alzheimer's disease , genetics , biology , medicine , disease
Background This study investigates the association between TOMM40 poly‐T length, age at onset, and neuropathology in individuals with Alzheimer's disease (AD) with the apolipoprotein E ( APOE ) ɛ3/ɛ3 allele. Methods Thirty‐two presenilin 1 ( PSEN1 ) mutation carriers with AD, 27 presenilin 2 ( PSEN2 ) mutation carriers with AD, 59 participants with late‐onset AD (LOAD), and 168 autopsied subjects from a community‐based cohort were genotyped for TOMM40 intron 6 poly‐T (rs10524523) length using short tandem repeat assays. Results Among AD individuals with PSEN2 mutations, the presence of a long poly‐T was associated with an earlier age at onset, whereas there were no such associations for subjects with PSEN1 mutations or LOAD. In community‐based participants, the presence of a long poly‐T was associated with increased neuritic tangles and a greater likelihood of pathologically diagnosed AD. Conclusion TOMM40 intron 6 poly‐T length may explain some of the variation in age at onset in PSEN2 familial AD and may be associated with AD neuropathology in persons with APOE ɛ3/ɛ3.