Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Alzheimers Dement. 2013 Sep;9(5):554-61. doi: 10.1016/j.jalz.2012.06.009. Epub 2012 Nov 22.
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) ε3/ε3 allele.
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.
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.
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 ε3/ε3.
本研究调查了载脂蛋白 E（APOE）ε3/ε3 等位基因的阿尔茨海默病（AD）个体中 TOMM40 多态性 T 长度、发病年龄和神经病理学之间的关联。
使用短串联重复序列分析，对 32 名早发性 AD 的早老素 1（PSEN1）突变携带者、27 名早发性 AD 的早老素 2（PSEN2）突变携带者、59 名晚发性 AD（LOAD）参与者和 168 名社区队列的尸检受试者进行 TOMM40 内含子 6 多态性 T（rs10524523）长度的基因分型。
在 PSEN2 突变的 AD 个体中，长多态性 T 与发病年龄较早有关，而 PSEN1 突变或 LOAD 受试者则无此关联。在社区参与者中，长多态性 T 与神经原纤维缠结增加和更有可能被病理诊断为 AD 有关。
TOMM40 内含子 6 多态性 T 长度可能解释了 PSEN2 家族性 AD 发病年龄的一些差异，并且可能与 APOE ε3/ε3 个体的 AD 神经病理学有关。
