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The microvascular extracellular matrix in brains with Alzheimer’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA)
Fluids and Barriers of the CNS ( IF 5.9 ) Pub Date : 2020-09-29 , DOI: 10.1186/s12987-020-00219-y
Mamatha Damodarasamy 1, 2 , Robert B Vernon 3 , Jasmine L Pathan 1 , C Dirk Keene 4 , Anthony J Day 5 , William A Banks 1, 2 , May J Reed 1, 2, 6
Affiliation  

Background The microvasculature (MV) of brains with Alzheimer’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA), in the absence of concurrent pathologies (e.g., infarctions, Lewy bodies), is incompletely understood. Objective To analyze microvascular density, diameter and extracellular matrix (ECM) content in association with ADNC and CAA. Methods We examined samples of cerebral cortex and isolated brain microvasculature (MV) from subjects with the National Institute on Aging-Alzheimer's Association (NIA-AA) designations of not-, intermediate-, or high ADNC and from subjects with no CAA and moderate-severe CAA. Cases for all groups were selected with no major (territorial) strokes, ≤ 1 microinfarct in screening sections, and no Lewy body pathology. MV density and diameter were measured from cortical brain sections. Levels of basement membrane (BM) ECM components, the protein product of TNF-stimulated gene-6 (TSG-6), and the ubiquitous glycosaminoglycan hyaluronan (HA) were assayed by western blots or HA ELISA of MV lysates. Results We found no significant changes in MV density or diameter among any of the groups. Levels of BM laminin and collagen IV (col IV) were lower in MV isolated from the high ADNC vs. not-ADNC groups. In contrast, BM laminin was significantly higher in MV from the moderate-severe CAA vs. the no CAA groups. TSG-6 and HA content were higher in the presence of both high ADNC and CAA, whereas levels of BM fibronectin and perlecan were similar among all groups. Conclusions Cortical MV density and diameter are not appreciably altered by ADNC or CAA. TSG-6 and HA are increased in both ADNC and CAA, with laminin and col IV decreased in the BM of high ADNC, but laminin increased in moderate-severe CAA. These results show that changes in the ECM occur in AD and CAA, but independently of one another, and likely reflect on the regional functioning of the brain microvasculature.

中文翻译:


阿尔茨海默病神经病理改变(ADNC)和脑淀粉样血管病(CAA)大脑中的微血管细胞外基质



背景 在没有并发病变(例如梗死、路易体)的情况下,患有阿尔茨海默病神经病理改变(ADNC)和脑淀粉样血管病(CAA)的大脑微血管(MV)尚不完全清楚。目的 分析微血管密度、直径和细胞外基质(ECM)含量与 ADNC 和 CAA 的关系。方法 我们检查了美国国家老龄化研究所-阿尔茨海默病协会 (NIA-AA) 指定的非、中度或高 ADNC 受试者以及无 CAA 和中度 ADNC 受试者的大脑皮层和分离脑微血管 (MV) 样本。严重CAA。所有组的病例均选择无重大(区域性)卒中、筛查切片中≤ 1 个微梗死且无路易体病理的病例。 MV 密度和直径是从皮质脑切片中测量的。通过 MV 裂解物的蛋白质印迹或 HA ELISA 测定基底膜 (BM) ECM 成分、TNF 刺激基因 6 (TSG-6) 的蛋白质产物和普遍存在的糖胺聚糖透明质酸 (HA) 的水平。结果 我们发现各组之间的 MV 密度或直径没有显着变化。与非 ADNC 组相比,从高 ADNC 组中分离出的 MV 中的 BM 层粘连蛋白和 IV 型胶原 (col IV) 水平较低。相反,中重度 CAA 组的 MV 中的 BM 层粘连蛋白显着高于无 CAA 组。在高 ADNC 和 CAA 存在的情况下,TSG-6 和 HA 含量较高,而所有组中 BM 纤连蛋白和基底膜聚糖的水平相似。结论 ADNC 或 CAA 并未明显改变皮质 MV 密度和直径。 TSG-6和HA在ADNC和CAA中均增加,在高ADNC的BM中层粘连蛋白和col IV减少,但在中重度CAA中层粘连蛋白增加。 这些结果表明,ECM 的变化发生在 AD 和 CAA 中,但彼此独立,并且可能反映了大脑微血管系统的区域功能。
更新日期:2020-09-29
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