Cognitive reserve, presynaptic proteins and dementia in the elderly.
Cognitive reserve, presynaptic proteins and dementia in the elderly.
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DOI：
10.1038/tp.2012.38
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发表时间：
2012-05-15
影响因子：
6.8
通讯作者：
Bennett DA
中科院分区：
文献类型：
--
作者：
Honer WG;Barr AM;Sawada K;Thornton AE;Morris MC;Leurgans SE;Schneider JA;Bennett DA
认知储备的差异可能导致具有类似数量的年龄相关神经病理学的人患痴呆症的可能性范围很广。突触前蛋白的数量和相互作用可能是认知储备的分子组成部分，有助于抵抗病理学表达为认知障碍。我们进行了一项前瞻性研究，每年评估N=253参与者没有痴呆症的研究进入。六种不同的突触前蛋白，以及突触体相关蛋白25（SNAP-25）和突触融合蛋白之间的蛋白质-蛋白质相互作用，在死后的大脑中进行了测量。我们评估了阿尔茨海默病（AD）病理学、脑梗死和突触前蛋白对痴呆几率、认知功能水平和皮质萎缩的贡献。N=97（38.3%）例患者存在临床痴呆，N=142（56.1%）例患者病理诊断为AD，N=77（30.4%）例患者存在脑梗死。在考虑AD病理和梗死后，囊泡相关膜蛋白、复合蛋白I和II以及SNAP-25/突触融合蛋白相互作用的量越大，痴呆的几率越低（比值比=0.36-0.68，P<0.001至P=0.03），认知功能越好（P<0.001至P=0.03）。更大的皮质萎缩，一种假定的痴呆生物标志物，与AD病理学无关，但与更低的复合蛋白II（P=0.01）和更低的SNAP-25/突触融合蛋白相互作用（P<0.001）相关。总之，大量的特定突触前蛋白和不同的蛋白质-蛋白质相互作用可能是认知储备的结构或功能成分，可降低老年痴呆症的风险。
Differences in cognitive reserve may contribute to the wide range of likelihood of dementia in people with similar amounts of age-related neuropathology. The amounts and interactions of presynaptic proteins could be molecular components of cognitive reserve, contributing resistance to the expression of pathology as cognitive impairment. We carried out a prospective study with yearly assessments of N=253 participants without dementia at study entry. Six distinct presynaptic proteins, and the protein–protein interaction between synaptosomal-associated protein 25 (SNAP-25) and syntaxin, were measured in post-mortem brains. We assessed the contributions of Alzheimer's disease (AD) pathology, cerebral infarcts and presynaptic proteins to odds of dementia, level of cognitive function and cortical atrophy. Clinical dementia was present in N=97 (38.3%), a pathologic diagnosis of AD in N=142 (56.1%) and cerebral infarcts in N=77 (30.4%). After accounting for AD pathology and infarcts, greater amounts of vesicle-associated membrane protein, complexins I and II and the SNAP-25/syntaxin interaction were associated with lower odds of dementia (odds ratio=0.36–0.68, P<0.001 to P=0.03) and better cognitive function (P<0.001 to P=0.03). Greater cortical atrophy, a putative dementia biomarker, was not associated with AD pathology, but was associated with lower complexin-II (P=0.01) and lower SNAP-25/syntaxin interaction (P<0.001). In conclusion, greater amounts of specific presynaptic proteins and distinct protein–protein interactions may be structural or functional components of cognitive reserve that reduce the risk of dementia with aging.
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