Possible Association between SNAP-25 Single Nucleotide Polymorphisms and Alterations of Categorical Fluency and Functional MRI Parameters in Alzheimer's Disease
Possible Association between SNAP-25 Single Nucleotide Polymorphisms and Alterations of Categorical Fluency and Functional MRI Parameters in Alzheimer's Disease
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DOI：
10.3233/jad-140057
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发表时间：
2014-01-01
影响因子：
4
通讯作者：
Clerici, Mario
中科院分区：
文献类型：
--
作者：
Guerini, Franca Rosa;Agliardi, Cristina;Clerici, Mario
突触体相关蛋白25 kDa(SNAP-25)是一种受年龄调节的囊泡圈套蛋白，参与突触的神经递质胞吐，这一过程在阿尔茨海默病(AD)中发生改变。SNAP-25水平的变化被认为是与年龄相关的认知功能下降的原因之一，SNAP-25基因的单核苷酸多态(SNPs)存在于神经精神疾病中，并在决定IQ表型中发挥作用。为了验证SNAP-25在AD中的可能作用，我们分析了AD患者(n=607)的五个基因多态性，并在148例遗忘性轻度认知障碍(AMCI)患者和两组年龄匹配的健康对照组(hc1：n=615和hc2：n=310)中重复了这项研究。结果显示，内含子rs363050(A)和rs363043(T)等位基因以及rs363050/rs363043 A-T单倍型在AD和aMCI中的分布频率显著高于对照组，且与AD的分类流利性病理评分相关。值得注意的是，功能磁共振分析表明，SNAP-25基因与扣带回、额叶(中回和上回)和颞顶(角回)区的脑活动显著降低有关。Snap-25基因多态性可能与阿尔茨海默病相关，并与分类流畅性改变和局部脑活动减少相关。Snap-25基因多态性可作为诊断AD和认知障碍的替代标志物；这些SNP也可能在AD的自然病程中起到预测作用。
Synaptosomal-associated protein of 25 kDa (SNAP-25) is an age-regulated vesicular SNARE protein involved in the exocytosis of neurotransmitters from synapses, a process that is altered in Alzheimer's disease (AD). Changes in SNAP-25 levels are suggested to contribute to age-related decline of cognitive function, and single nucleotide polymorphisms (SNPs) in the SNAP-25 gene are present in neuropsychiatric conditions and play a role in determining IQ phenotypes. To verify a possible role of SNAP-25 in AD, we analyzed five gene polymorphisms in patients with AD (n = 607), replicating the study in subjects with amnestic mild cognitive impairment (aMCI) (n = 148) and in two groups of age-matched healthy controls (HC1: n = 615 and HC2: n = 310). Results showed that the intronic rs363050 (A) and rs363043 (T) alleles, as well as the rs363050/rs363043 A-T haplotype are significantly more frequent in AD and aMCI and are associated with pathological scores of categorical fluency in AD. Notably, functional MRI analyses indicated that SNAP-25 genotypes correlate with a significantly decreased brain activity in the cingulate cortex and in the frontal (middle and superior gyri) and the temporo-parietal (angular gyrus) area. SNAP-25 polymorphisms may be associated with AD and correlate with alterations in categorical fluency and a reduced localized brain activity. SNAP-25 polymorphisms could be used as surrogate markers for the diagnosis of AD and of cognitive deficit; these SNPs might also have a possible predictive role in the natural history of AD.