Loss of capillary pericytes and the blood-brain barrier in white matter in poststroke and vascular dementias and Alzheimer's disease.
Loss of capillary pericytes and the blood-brain barrier in white matter in poststroke and vascular dementias and Alzheimer's disease.
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DOI：
10.1111/bpa.12888
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Kalaria RN
中科院分区：
文献类型：
--
作者：
Ding R;Hase Y;Ameen-Ali KE;Ndung'u M;Stevenson W;Barsby J;Gourlay R;Akinyemi T;Akinyemi R;Uemura MT;Polvikoski T;Mukaetova-Ladinska E;Ihara M;Kalaria RN
白色物质（WM）疾病与神经胶质血管单位的破坏有关，其涉及血脑屏障（BBB）的破坏。我们量化周细胞作为胶质血管单位的组成部分，并评估其在血管性痴呆和其他常见痴呆中的地位。免疫组织化学和免疫荧光方法被开发来评估的分布和定量的周细胞连接到额叶WM毛细血管。通过胶原蛋白4（COL 4）和血小板衍生生长因子受体-β（PDGFR-β）抗体鉴定具有细胞核的周细胞，并使用PDGFR-β特异性ELISA进行进一步验证。我们评估了总共124例卒中后痴呆（PSD）、血管性痴呆（VaD）、阿尔茨海默病（AD）、AD-VaD（混合型）和卒中后非痴呆（PSND）卒中幸存者以及正常老年对照受试者的死后大脑。COL 4和PDGFR-β反应性周细胞在毛细血管壁周围采用特征性的“新月形”或结节状形状。我们估计，在年轻和老年对照组中，周细胞胞体的密度分别为225 ±38和200 ±13（SEM）/COL 4 mm 2面积或2.0 ± 0.1和1.7 ± 0.1/mm毛细血管长度。值得注意的是，与PSND和对照组相比，PSD、VaD、混合型和AD受试者额叶中的WM周细胞减少约35%-45%（P < 0.001）。我们还发现周细胞数量与WM中的PDGFR-β反应性相关。我们的研究结果首先证明了一种可靠的方法来量化COL 4阳性周细胞，然后表明，在不同的痴呆症中，包括PSD，VaD，混合型和AD，深层WM周细胞减少。我们的研究结果表明，周细胞的下调与几种衰老相关性痴呆中深层WM中BBB的破坏有关。
White matter (WM) disease is associated with disruption of the gliovascular unit, which involves breach of the blood–brain barrier (BBB). We quantified pericytes as components of the gliovascular unit and assessed their status in vascular and other common dementias. Immunohistochemical and immunofluorescent methods were developed to assess the distribution and quantification of pericytes connected to the frontal lobe WM capillaries. Pericytes with a nucleus were identified by collagen 4 (COL4) and platelet‐derived growth factor receptor‐β (PDGFR‐β) antibodies with further verification using PDGFR‐β‐specific ELISA. We evaluated a total of 124 post‐mortem brains from subjects with post‐stroke dementia (PSD), vascular dementia (VaD), Alzheimer’s disease (AD), AD‐VaD (Mixed) and post‐stroke non‐demented (PSND) stroke survivors as well as normal aging controls. COL4 and PDGFR‐β reactive pericytes adopted the characteristic “crescent” or nodule‐like shapes around capillary walls. We estimated densities of pericyte somata to be 225 ±38 and 200 ±13 (SEM) per COL4 mm2 area or 2.0 ± 0.1 and 1.7 ± 0.1 per mm capillary length in young and older aging controls. Remarkably, WM pericytes were reduced by ~35%–45% in the frontal lobe of PSD, VaD, Mixed and AD subjects compared to PSND and controls subjects (P < 0.001). We also found pericyte numbers were correlated with PDGFR‐β reactivity in the WM. Our results first demonstrate a reliable method to quantify COL4‐positive pericytes and then, indicate that deep WM pericytes are decreased across different dementias including PSD, VaD, Mixed and AD. Our findings suggest that downregulation of pericytes is associated with the disruption of the BBB in the deep WM in several aging‐related dementias.
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影响因子：
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作者：
Chen A;Oakley AE;Monteiro M;Tuomela K;Allan LM;Mukaetova-Ladinska EB;O'Brien JT;Kalaria RN
通讯作者：
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发表时间：
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期刊：
BMJ (Clinical research ed.)
影响因子：
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10.1093/brain/awv328
发表时间：
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期刊：
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影响因子：
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影响因子：
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影响因子：
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作者：
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