- Brain Pathology（Fu、Josephs 等，梅奥诊所）：4 例对照、3 例 PSP、3 例 CBD 尸检脑，取额上/额中回与基底节，以 IV 型胶原、MCT1、αSMA 标记血管，共聚焦定量血管周围 GFAP、Iba1、CD68。
- PSP 与 CBD 都有广泛的血管周围促炎改变，CBD 更重：CBD 累及额叶与基底节，以额叶白质为主；PSP 主要在基底节。
- 血管类型不同：CBD 小动脉与小静脉受累相当，PSP 以小静脉为主；区域分布与两病的特征性受累脑区一致。
- 解读提示：样本量很小（每组 3–4 例），属探索性研究；提示血管周围炎症可能参与 4R tau 病的发病。本站仅获摘要。
收录范围：PubMed 摘要中英对照。原文为 Wiley 开放获取（CC BY），但出版社页面被 Cloudflare 拦截，本站未获全文与图表。
摘要
进行性核上性麻痹（PSP）与皮质基底节变性（CBD）都是以 4 重复（4R）tau 蛋白聚集为特征的神经退行性疾病。二者神经病理特征和典型临床症状各不相同，但体征与症状互有重叠。越来越多的证据表明，免疫应答失调是神经退行性变的重要促成因素，但其在 4R tau 病中的作用尚不明确。本研究旨在从血管角度探讨神经炎症在 4R tau 病中的参与情况。
评估了 4 例对照、3 例 PSP 和 3 例 CBD 的尸检标本，取材部位为额上/额中回（S/M-FG）和基底节（BG）。免疫荧光染色包括神经炎症标志物：胶质纤维酸性蛋白（GFAP）、离子钙结合衔接分子 1（Iba1）、CD68；血管标志物：IV 型胶原（ColIV）、单羧酸转运体 1（MCT1）和 α-平滑肌肌动蛋白（αSMA）。以血管的共聚焦 z 轴叠层最大投影图像为掩膜，定量血管周围 GFAP+/Iba1+/CD68+ 标记总量；并对 MCT1 与 αSMA 双标的动脉和静脉计算 GFAP 免疫反应性比值，以进一步区分小静脉与小动脉在促炎活化中的受累程度。
PSP 和 CBD 均有广泛的血管周围促炎改变，CBD 更重。CBD 中活化的 GFAP+ 星形胶质细胞和小胶质细胞/巨噬细胞广泛分布于 S/M-FG 和 BG，以 S/M-FG 白质受累更重；PSP 的神经炎症则主要见于 BG。两种 4R tau 病受累的血管类型不同：CBD 小动脉与小静脉的促炎改变程度相当，PSP 则以小静脉促炎为主。
PSP 与 CBD 血管周围促炎改变的区域分布不同，与各自的特征性受累脑区相对应。CBD 的血管周围促炎改变更严重，累及小动脉和小静脉；PSP 则以小静脉受累为主。血管周围促炎可能是 4R tau 病的关键病理生理过程。
- Brain Pathology (Fu, Josephs and colleagues, Mayo Clinic): autopsy brains from 4 controls, 3 PSP and 3 CBD; superior/middle frontal gyrus and basal ganglia; vessels labelled with collagen IV, MCT1 and αSMA, and perivascular GFAP, Iba1 and CD68 quantified by confocal imaging.
- Both PSP and CBD showed widespread perivascular proinflammatory change, greater in CBD: CBD involved frontal cortex and basal ganglia with frontal white matter most affected, whereas PSP was concentrated in the basal ganglia.
- Vessel type differed: CBD affected arterioles and venules comparably, PSP predominantly venules; the regional pattern matched each disease’s characteristic distribution.
- Interpretation: a very small exploratory series (3–4 cases per group) suggesting perivascular inflammation may contribute to 4R tauopathy. Abstract only.
Scope: the PubMed abstract. The article is Wiley open access (CC BY), but the publisher page was blocked by Cloudflare for our fetcher, so the full text and figures were not obtained.
Abstract
Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are both neurodegenerative diseases characterized by aggregates composed of 4-repeat (4R) tau protein. They have distinct neuropathological features and classic clinical symptoms; however, the signs and symptoms overlap across the two syndromes. Accumulating evidence suggests that dysregulated immune response is a major contributing factor to neurodegeneration but its role in 4R-tauopathies remains undetermined. The aim is to explore the involvement of neuroinflammation from a vascular perspective in 4R-tauopathies.
Autopsies from four controls, three PSP, and three CBD cases were assessed. Samples were obtained from the superior/middle frontal gyrus (S/M-FG) and basal ganglia (BG). Immunofluorescence staining included neuroinflammatory markers: glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba1), cluster of differentiation 68 (CD68); vascular markers: collagen type IV (ColIV), monocarboxylate transporter-1 (MCT1), and α-smooth muscle actin (αSMA). Maximally projected confocal z-stack images of vasculature were used as a mask to quantify total perivascular GFAP+/Iba1+/CD68+ labeling. GFAP immunoreactivity ratio between MCT1 and αSMA double labeled arteries and veins was quantified to further differentiate venular and arteriolar involvement into proinflammatory activation.
Both PSP and CBD had widespread perivascular proinflammatory changes, although greater in CBD. The activated GFAP+ astrocytes and microglia/macrophages in CBD were distributed extensively in S/M-FG and BG, with S/M-FG WM more affected. In PSP, abundant neuroinflammation was found in BG. The involvement of vasculature type was distinct among the two 4R-tauopathies, while CBD showed comparable proinflammatory changes in arterioles and venules, PSP exhibited predominant proinflammation in venules.
The regional pattern of perivascular proinflammation differed between PSP and CBD, corresponding to the characteristic affected brain regions. CBD had more severe perivascular proinflammation that involved both arterioles and venules, while venules were more affected in PSP. Perivascular proinflammation may be a critical pathophysiological process in 4R-tauopathies.