QUANTITATIVE SYNAPTIC ALTERATIONS IN THE HUMAN NEOCORTEX DURING NORMAL AGING

QUANTITATIVE SYNAPTIC ALTERATIONS IN THE HUMAN NEOCORTEX DURING NORMAL AGING
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DOI:
10.1212/wnl.43.1_part_1.192
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发表时间:
1993-01-01
期刊:
影响因子:
9.9
通讯作者:
TERRY, RD
TERRY, RD
中科院分区:
医学1区
文献类型:
--
作者:
MASLIAH, E;MALLORY, M;TERRY, RD

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我们使用β/A4淀粉样蛋白和突触素双重免疫标记的切片,对25名16至98岁的非痴呆个体的额叶皮质中的突触群体密度进行了定量,发现突触前末梢(PT)计数与年龄之间存在显著的负相关性(r =-0.7,p < 0.001)。与60岁以下的人相比,60岁以上的人PT密度平均下降20%。年龄与β/A4淀粉样蛋白阳性斑块数量或突触密度与淀粉样蛋白斑块数量之间无显著相关性。数字化航空光学图像的进一步分析显示,在正常老年病例的成熟斑块中存在突触丢失的局灶性区域和膨胀的含突触素的终扣。然而,我们发现弥散斑内外的突触内容物没有微观变化。我们认为,在新皮层的突触输入的损失是一个年龄依赖性因素,有助于整体的突触损失在阿尔茨海默病,但这可能是在很大程度上独立的β/A4-淀粉样蛋白沉积。
We quantified the synaptic population density in the frontal cortex of 25 individuals without dementia 16 to 98 years old, using sections double-immunolabeled for beta/A4 amyloid and for synaptophysin, and found a significant inverse correlation between the presynaptic terminal (PT) counts and age (r = -0.7, p < 0.001). Individuals older than 60 years had an average 20% decrease in PT density compared with individuals younger than 60 years. There were no significant correlations between the age and the number of beta/A4 amyloid-positive plaques or between synaptic density and the number of amyloid plaques. Further analysis of the digitized aerial optical images showed focal areas of synapse loss and distended synaptophysin-containing boutons in the mature plaques of the normal aged cases. However, we found no microscopic changes in the synaptic content inside and outside the diffuse plaques. We suggest that a loss of synaptic input in the neocortex is an age-dependent factor that contributes to the overall synaptic loss in Alzheimer's disease, but that this might be largely independent of the beta/A4-amyloid deposition.