Brain mural cell loss in the parietal cortex in Alzheimer's disease correlates with cognitive decline and TDP-43 pathology.
Brain mural cell loss in the parietal cortex in Alzheimer's disease correlates with cognitive decline and TDP-43 pathology.
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阿尔茨海默氏病的顶叶皮层中的脑壁细胞损失与认知能力下降和TDP-43病理相关。
DOI：
10.1111/nan.12599
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发表时间：
2020-08
影响因子：
5
通讯作者：
Calon F
中科院分区：
文献类型：
--
作者：
Bourassa P;Tremblay C;Schneider JA;Bennett DA;Calon F
脑壁细胞（BMC）、平滑肌细胞和周细胞与内皮细胞密切相互作用，并调节多种脑血管功能。BMC功能的丧失被怀疑在阿尔茨海默病（AD）的病理生理学中起作用。BMC标志物，即平滑肌细胞的平滑肌α肌动蛋白（α-SMA），以及周细胞的血小板衍生生长因子受体β（PDGFRβ）和氨肽酶N（ANPEP或CD 13），通过Western免疫印迹法在宗教教团研究的60名参与者的顶叶皮质微血管提取物中进行评估，死亡年龄范围为75至98岁。临床诊断为AD的参与者的α-SMA、PDGFRβ和CD 13血管水平较低。这些降低与整体认知、情景和语义记忆、感知速度和视觉空间能力的认知评分降低相关。此外，α-SMA、PDGFRβ和CD 13与血管Aβ40浓度呈负相关。BMC标记物的血管水平也与皮质匀浆中裂解的不溶性磷酸化反式反应DNA结合蛋白43（TDP-43）（25 kDa）呈负相关，与裂解的可溶性磷酸化TDP-43（35 kDa）呈正相关，表明BMC损失与裂解的磷酸化TDP-43聚集之间存在强相关性。这项研究的结果强调了AD中BMC的损失。a-SMA、PDGFRβ和CD 13血管水平与认知评分、TDP-43聚集和顶叶皮质中Aβ的脑血管蓄积之间的相关性表明，BMC损失有助于AD症状和病理学，进一步加强了脑血管缺陷与痴呆之间的联系。
Brain mural cells (BMC), smooth muscle cells and pericytes, interact closely with endothelial cells and modulate numerous cerebrovascular functions. A loss of BMC function is suspected to play a role in the pathophysiology of Alzheimer’s Disease (AD). BMC markers, namely smooth muscle alpha actin (α-SMA) for smooth muscle cells, as well as platelet-derived growth factor receptor β (PDGFRβ) and aminopeptidase N (ANPEP or CD13) for pericytes, were assessed by Western immunoblotting in microvessel extracts from the parietal cortex of 60 participants of the Religious Orders study, with ages at death ranging from 75 to 98 years old. Participants clinically diagnosed with AD had lower vascular levels of α-SMA, PDGFRβ and CD13. These reductions were correlated with lower cognitive scores for global cognition, episodic and semantic memory, perceptual speed and visuospatial ability. In addition, α-SMA, PDGFRβ and CD13 were negatively correlated with vascular Aβ40 concentrations. Vascular levels of BMC markers were also inversely correlated with cleaved insoluble phosphorylated transactive response DNA binding protein 43 (TDP-43) (25 kDa) and positively correlated with cleaved soluble phosphorylated TDP-43 (35 kDa) in cortical homogenates, suggesting strong association between BMC loss and cleaved phosphorylated TDP-43 aggregation. The results of this study highlight a loss of BMC in AD. The associations between a-SMA, PDGFRβ and CD13 vascular levels with cognitive scores, TDP-43 aggregation and cerebrovascular accumulation of Aβ in the parietal cortex suggest that BMC loss contributes to both AD symptoms and pathology, further strengthening the link between cerebrovascular defects and dementia.
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影响因子：
3.7
作者：
Bories C;Guitton MJ;Julien C;Tremblay C;Vandal M;Msaid M;De Koninck Y;Calon F
通讯作者：
Calon F
影响因子：
11.2
作者：
Bennett, David A.;Wilson, Robert S.;Boyle, Patricia A.;Buchman, Aron S.;Schneider, Julie A.
通讯作者：
Schneider, Julie A.
DOI：
10.3233/jad-179939
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Bennett DA;Buchman AS;Boyle PA;Barnes LL;Wilson RS;Schneider JA
通讯作者：
Schneider JA
影响因子：
4.8
作者：
Aldea, Roxana;Weller, Roy O.;Richardson, Giles
通讯作者：
Richardson, Giles
DOI：
10.1097/00005072-199804000-00008
发表时间：
1998-04-01
影响因子：
3.2
作者：
Alonzo, NC;Hyman, BT;Greenberg, SM
通讯作者：
Greenberg, SM