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

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• 作者：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
• 关键词：Alzheimer&rsquo ; s disease ; Age at onset ; Genetic ; APOE ; TOMM40 ; PSEN1 mutation ; PSEN2 mutation ; Neuropathology
• 刊名：Alzheimer's Dementia
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：9
• 期：5
• 页码：554-561
• 全文大小：379 K

文摘

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.