TOMM40 intron 6 poly‐T length, age at onset, and neuropathology of AD in individuals with APOE ɛ3/ɛ3

• DOI: 10.1016/j.jalz.2012.06.009
• Publication Date: 2012-11-23T00:33:41Z
• Authors: Ge Li; Lynn M. Bekris; Lesley Leong; Ellen J. Steinbart; Jane B. Shofer; Paul K. Crane; Eric B. Larson; Elaine R. Peskind; Thomas D. Bird; Chang‐En Yu
• Keywords: Adult; Aged, 80 and over; Male; 0301 basic medicine; Genotype; Poly T; Apolipoprotein E3; Membrane Transport Proteins; Middle Aged; Introns; 03 medical and health sciences; Alzheimer Disease; Mitochondrial Precursor Protein Import Complex Proteins; Mutation; Presenilin-2; Presenilin-1; Humans; Female; Genetic Predisposition to Disease; Age of Onset; Aged

AbstractBackgroundThis 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.MethodsThirty‐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.ResultsAmong 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.ConclusionTOMM40 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.