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.

中文翻译：

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中风后、血管性痴呆和阿尔茨海默病中毛细血管周细胞和白质中血脑屏障的丧失。

白质 (WM) 疾病与胶质血管单元的破坏有关，涉及血脑屏障 (BBB) 的破坏。我们将周细胞量化为胶质血管单元的组成部分，并评估它们在血管和其他常见痴呆症中的状态。开发了免疫组织化学和免疫荧光方法来评估连接到额叶 WM 毛细血管的周细胞的分布和定量。通过胶原蛋白 4 (COL4) 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 进一步验证。我们评估了来自卒中后痴呆 (PSD)、血管性痴呆 (VaD)、阿尔茨海默病 (AD)、AD-VaD（混合）和中风后非痴呆（PSND）中风幸存者以及正常衰老对照。COL4 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。我们估计周细胞胞体的密度为每 COL4 mm 225 ±38 和 200 ±13 (SEM)²面积或 2.0 ± 0.1 和 1.7 ± 0.1 每毫米毛细血管长度在年轻和年长的老化控制。值得注意的是，与 PSND 和对照受试者相比，PSD、VaD、混合和 AD 受试者的额叶中的 WM 周细胞减少了约 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。我们的结果首先证明了一种量化 COL4 阳性周细胞的可靠方法，然后表明深 WM 周细胞在不同痴呆症（包括 PSD、VaD、混合和 AD）中减少。我们的研究结果表明，周细胞的下调与几种与衰老相关的痴呆症中深部 WM 中 BBB 的破坏有关。