TOMM40 intron 6 poly-T length, age at onset, and neuropathology of AD in individuals with APOE ?3/?3.

ABSTRACT: 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) ?3/?3 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 ?3/?3.

SUBMITTER: Li G 

PROVIDER: S-EPMC3606272 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature