Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC, USA.
Alzheimers Dement. 2012 Sep;8(5):381-8. doi: 10.1016/j.jalz.2011.10.005. Epub 2012 Aug 3.
A highly polymorphic T homopolymer was recently found to be associated with late-onset Alzheimer's disease risk and age of onset.
To explore the effects of the polymorphic polyT tract (rs10524523, referred as '523') on cognitive performance in cognitively healthy elderly individuals.
One hundred eighty-one participants were recruited from local independent-living retirement communities. Informed consent was obtained, and participants completed demographic questionnaires, a conventional paper-and-pencil neuropsychological battery, and the computerized Cambridge Neuropsychological Test Automated Battery (CANTAB). Saliva samples were collected for determination of the TOMM40 '523' (S, L, VL) and the apolipoprotein E (APOE) (ɛ2, 3, 4) genotypes. From the initial sample of 181 individuals, 127 were eligible for the association analysis. Participants were divided into three groups based on '523' genotypes (S/S, S/L-S/VL, and L/L-L/VL-VL/VL). Generalized linear models were used to evaluate the association between the '523' genotypes and neuropsychological test performance. Analyses were adjusted for age, sex, education, depression, and APOE ɛ4 status. A planned subanalysis was undertaken to evaluate the association between '523' genotypes and test performance in a sample restricted to APOE ɛ3 homozygotes.
The S homozygotes performed better, although not significantly, than the S/L-S/VL and the VL/L-L/VL-VL/VL genotype groups on measures associated with memory (CANTAB Paired Associates Learning, Verbal Recognition Memory free recall) and executive function (CANTAB measures of Intra-Extra Dimensional Set Shift). Follow-up analysis of APOE ɛ3 homozygotes only showed that the S/S group performed significantly better than the S/VL group on measures of episodic memory (CANTAB Paired Associates Learning and Verbal Recognition Memory free recall), attention (CANTAB Rapid Visual Information Processing latency), and executive function (Digit Symbol Substitution). The S/S group performed marginally better than the VL/VL group on Intra-Extra Dimensional Set Shift. None of the associations remained significant after applying a Bonferroni correction for multiple testing.
Results suggest important APOE-independent associations between the TOMM40 '523' polymorphism and specific cognitive domains of memory and executive control that are preferentially affected in early-stage Alzheimer's disease.
最近发现一个高度多态性的 T 串联重复序列与晚发性阿尔茨海默病风险和发病年龄有关。
探讨多态性聚 T 重复序列（rs10524523，称为“523”）对认知健康老年人认知表现的影响。
从当地独立生活的退休社区招募了 181 名参与者。获得了知情同意，参与者完成了人口统计学问卷、传统的纸笔神经心理学测试和计算机化的剑桥神经心理学测试自动化电池（CANTAB）。收集唾液样本以确定 TOMM40“523”（S、L、VL）和载脂蛋白 E（APOE）（ɛ2、3、4）基因型。在最初的 181 名参与者中，有 127 名符合关联分析的条件。根据“523”基因型（S/S、S/L-S/VL 和 L/L-L/VL-VL/VL）将参与者分为三组。使用广义线性模型评估“523”基因型与神经心理学测试表现之间的关联。分析调整了年龄、性别、教育、抑郁和 APOE ɛ4 状态。进行了一项计划的亚分析，以评估在仅为 APOE ɛ3 纯合子的样本中“523”基因型与测试表现之间的关联。
S 纯合子在与记忆（CANTAB 配对关联学习、言语识别记忆自由回忆）和执行功能（CANTAB 内-外维度集转换的测量）相关的测量上表现优于 S/L-S/VL 和 VL/L-L/VL-VL/VL 基因型组，尽管差异不显著。对 APOE ɛ3 纯合子的进一步分析仅表明，S/S 组在情节记忆（CANTAB 配对关联学习和言语识别记忆自由回忆）、注意力（CANTAB 快速视觉信息处理潜伏期）和执行功能（数字符号替代）方面的表现明显优于 S/VL 组。S/S 组在内外维度集转换方面的表现略优于 VL/VL 组。在进行多次测试的 Bonferroni 校正后，没有一项关联仍然显著。
结果表明，TOMM40“523”多态性与记忆和执行控制等特定认知领域之间存在重要的 APOE 独立关联，这些认知领域在早期阿尔茨海默病中优先受到影响。
