Accumulation of SNAP-25 immunoreactive material in axons of Alzheimer's disease
Accumulation of SNAP-25 immunoreactive material in axons of Alzheimer's disease
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DOI：
10.1097/00001756-199712010-00006
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发表时间：
1997-12-01
期刊：
影响因子：
1.7
通讯作者：
Duyckaerts, C
中科院分区：
文献类型：
--
作者：
Dessi, F;Colle, MA;Duyckaerts, C
神经纤维缠结和神经纤维丝都是由过度磷酸化的tau蛋白组成，表明阿尔茨海默病中微管的改变。本研究的目的是测试轴浆流，这是依赖于完整的微管组装这些病变的后果。我们评估了运输的突触蛋白从神经元细胞体的轴突终端，使用SNAP-25（突触体相关蛋白25 kD）作为受损的轴突运输的标志物的免疫组织化学。从29名年龄超过75岁的个体中获得了缘上回的样本，这些个体的认知功能已经进行了前瞻性评估。在严重痴呆个体的白色物质中观察到肿胀轴突中的免疫反应性物质积聚，其数量与神经元缠结的密度（r = 0.53，p = 0.005）和局灶性A β沉积物的密度（r = 0.61，p = 0.001）相关。这支持了阿尔茨海默病中细胞骨架功能障碍的假设。一个意想不到的发现是灰质中SNAP-25免疫组织化学与智力状态或神经元缠结密度、局灶性A β沉积和神经元分布之间缺乏相关性。这些结果质疑突触标记物作为痴呆症相关因素的作用，应该扩展到其他大脑区域。
NEUROFIBRILLARY tangles and neuropil threads, both made of hyperphosphorylated tau proteins, point to an alteration of microtubules in Alzheimer's disease. The aim of this study was to test the consequences of these lesions on axoplasmic flow, which is dependent on intact microtubule assembly. We assessed the transport of synaptic proteins from the neuronal cell body to axonal terminals, using SNAP-25 (synaptosomal-associated protein of 25 kD) immunohistochemistry as a marker of impaired axonal transport. A sample from the supramarginalis gyrus was obtained from 29 individuals over 75 years of age whose cognitive function had been prospectively assessed. Accumulation of immunoreactive material in swollen axons was observed in the white matter of severely demented individuals, and their number was correlated with the density of neurofibrillary tangles (r = 0.53, p = 0.005) and of focal A beta deposits (r = 0.61, p = 0.001). This supports the hypothesis of a dysfunction of the cytoskeleton in Alzheimer's disease. An unexpected finding was the lack of correlation between SNAP-25 immunohistochemistry in the grey matter and the intellectual status or the density of neurofibrillary tangles, focal A beta deposits and neuronal profiles. These results which question the role of synaptic markers as correlates of dementia, should be extended to other brain areas.