Longitudinal modeling of cognitive aging and the TOMM40 effect.
Longitudinal modeling of cognitive aging and the TOMM40 effect.
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DOI：
10.1016/j.jalz.2011.11.006
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Roses AD
中科院分区：
文献类型：
--
作者：
Caselli RJ;Dueck AC;Huentelman MJ;Lutz MW;Saunders AM;Reiman EM;Roses AD
TOMM 40（线粒体外膜孔亚基转位酶）与载脂蛋白E（APOE）处于连锁不平衡状态。APOE e4与TOMM 40内含子6内的长（L; 21-29个T残基）多聚T变体连接，而APOE e3可与短（S; <21个T残基）或非常长（VL; >29个T残基）变体相关。为了评估TOMM 40对阿尔茨海默病（AD）发病的可能贡献，我们比较了TOMM 40和APOE基因型对临床前纵向记忆衰退的影响。639名年龄在21-97岁之间、具有已知TOMM 40基因型的认知正常个体的APOE e4富集队列每两年进行一次纵向神经心理学测试。我们估计的纵向效应的年龄记忆使用的统计模型，同时模拟横向和纵向效应的年龄对听觉言语学习测试长期记忆评分（AVLT）的APOE，TOMM 40，两者之间的相互作用。TOMM 40（p=0.04线性效应，p=0.03二次效应）和APOE（p=0.06线性效应，p=0.008二次效应）总体上存在显著效应，无显著相互作用（p=0.63）。这些差异是年龄依赖性的：60岁之前有显著的TOMM 40效应（p=0.009），其特征是平坦的重测改善（仅VL/VL亚组），但无显著的APOE效应; 60岁之后有显著的APOE效应（p=0.006），其特征是记忆力加速下降（e4携带者），但无显著的TOMM 40效应。TOMM 40和APOE都显著影响与年龄相关的记忆表现，但似乎彼此独立。
TOMM40 (translocase of the outer mitochondrial membrane pore subunit) is in linkage disequilibrium with apolipoprotein E (APOE). APOE e4 is linked to long (L; 21–29 T residues) poly-T variants within intron 6 of TOMM40 while APOE e3 can be associated with either with a short (S; <21 T residues) or very long (VL; >29 T residues) variant. To assess the possible contribution of TOMM40 to Alzheimer’s disease (AD) onset, we compared the effects of TOMM40 and APOE genotype on preclinical longitudinal memory decline. An APOE e4 enriched cohort of 639 cognitively normal individuals age 21–97 years of known TOMM40 genotype underwent longitudinal neuropsychological testing every two years. We estimated the longitudinal effect of age on memory using statistical models that simultaneously modeled cross sectional and longitudinal effects of age on the auditory verbal learning test long term memory score (AVLT) by APOE, TOMM40, and the interaction between the two. There were significant effects overall for both TOMM40 (p=0.04 linear effect, p=0.03 quadratic effect) and APOE (p=0.06 linear effect, p=0.008 quadratic effect) with no significant interaction (p=0.63). These differences were age-dependent: there was a significant TOMM40 effect prior to age 60 (p=0.009) characterized by flattened test-retest improvement (VL/VL subgroup only) but no significant APOE effect; and a significant APOE effect after age 60 (p=0.006) characterized by accelerated memory decline (e4 carriers) but no significant TOMM40 effect. Both TOMM40 and APOE significantly influence age-related memory performance, but appear to do so independently of each other.
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影响因子：
4.8
作者：
Chen, Hung-Kai;Ji, Zhong-Sheng;Mahley, Robert W.
通讯作者：
Mahley, Robert W.
影响因子：
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作者：
Cruchaga, Carlos;Nowotny, Petra;Goate, Alison M.
通讯作者：
Goate, Alison M.
影响因子：
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作者：
Li, Hao;Wetten, Sally;Roses, Allen D.
通讯作者：
Roses, Allen D.
影响因子：
4.2
作者：
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通讯作者：
Gibson, Guy E.
影响因子：
5
作者：
WARE, JH;DOCKERY, DW;SPEIZER, FE
通讯作者：
SPEIZER, FE