Dendritic spine remodeling accompanies Alzheimer's disease pathology and genetic susceptibility in cognitively normal aging.
Dendritic spine remodeling accompanies Alzheimer's disease pathology and genetic susceptibility in cognitively normal aging.
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DOI：
10.1016/j.neurobiolaging.2018.09.003
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发表时间：
2019-01
影响因子：
4.2
通讯作者：
Herskowitz JH
中科院分区：
文献类型：
--
作者：
Boros BD;Greathouse KM;Gearing M;Herskowitz JH
树突棘形态的细微改变可以对神经元回路的连接模式和随后的认知行为产生显著影响。过去对啮齿动物和非人类灵长类动物衰老的研究表明，脊柱密度的减少伴随着前额皮质锥体神经元脊柱形态的改变。在本报告中，我们对40-94岁认知正常个体的背外侧前额叶皮层树突棘的三维形态进行了可视化和数字重建。线性模型定义了脊柱与年龄、最小精神状态检查（MMSE）、APOE ε4等位基因状态和阿尔茨海默病（AD）病理之间的关系。与其他哺乳动物的研究结果相似，脊柱密度与人类衰老呈负相关。脊柱头直径减小与MMSE评分增高相关。携带APOE ε4等位基因的个体表现出更多的树突丝状足和细棘结构改变。AD病理的存在与脊柱长度增加、细棘头直径减小和丝状足密度增加有关。我们的研究揭示了前额叶皮层的脊柱形态如何随着人类衰老而变化，并强调了选择性脊柱群体的关键结构改变，这些改变可能促进认知正常功能，尽管APOE ε4等位基因或AD病理。
Subtle alterations in dendritic spine morphology can induce marked effects on connectivity patterns of neuronal circuits and subsequent cognitive behavior. Past studies of rodent and non-human primate aging revealed reductions in spine density with concomitant alterations in spine morphology among pyramidal neurons in the prefrontal cortex. In this report, we visualized and digitally reconstructed the three-dimensional morphology of dendritic spines from the dorsolateral prefrontal cortex in cognitively normal individuals aged 40–94 years. Linear models defined relationships between spines and age, Mini–Mental State Examination (MMSE), APOE ε4 allele status, and Alzheimer’s disease (AD) pathology. Similar to findings in other mammals, spine density correlated negatively with human aging. Reduced spine head diameter associated with higher MMSE scores. Individuals harboring an APOE ε4 allele displayed greater numbers of dendritic filopodia and structural alterations in thin spines. The presence of AD pathology correlated with increased spine length, reduced thin spine head diameter, and increased filopodia density. Our study reveals how spine morphology in the prefrontal cortex changes in human aging and highlights key structural alterations in selective spine populations that may promote cognitively normal function despite harboring the APOE ε4 allele or AD pathology.
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影响因子：
17.1
作者：
Finnema, Sjoerd J.;Nabulsi, Nabeel B.;Carson, Richard E.
通讯作者：
Carson, Richard E.
影响因子：
3.3
作者：
Dickstein, D. L.;Weaver, C. M.;Luebke, J. I.;Hof, P. R.
通讯作者：
Hof, P. R.
DOI：
10.1023/a:1024134312173
发表时间：
2002-03-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
Benavides-Piccione, R;Ballesteros-Yáñez, I;Yuste, R
通讯作者：
Yuste, R
影响因子：
16.2
作者：
Holtmaat, AJGD;Trachtenberg, JT;Svoboda, K
通讯作者：
Svoboda, K
影响因子：
2
作者：
Holmes, TJ;O'Connor, NJ
通讯作者：
O'Connor, NJ