血管周围磷酸化 TDP-43 包涵体与阿尔茨海默病的病理以及 CD146 和 Aquaporin-4 的缺失有关

IF 5.8 2区 医学 Q1 CLINICAL NEUROLOGY
Brain Pathology Pub Date : 2024-09-09 DOI:10.1111/bpa.13304
Jessica Santiago, Dovilė Pocevičiūtė, , Malin Wennström
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引用次数: 0

摘要

大多数阿尔茨海默氏症(AD)患者的海马体中都有跨活性反应 DNA 结合蛋白 43(TDP-43)的聚集体,这与疾病的恶化有关。TDP-43 包涵体通常存在于神经元中,但也存在于星形胶质细胞中。星形胶质细胞中的 TDP-43 包涵体的影响尚不清楚。在本研究中,我们调查了星形胶质细胞内膜中磷酸化 TDP-43 (pTDP-43)包涵体的存在及其与血脑屏障(BBB)损伤、淋巴系统功能障碍和 AD 病理学的潜在联系。通过用 TDP-43 和 pTDP-43 以及星形胶质细胞标记物胶质纤维酸性蛋白(GFAP)对阿氏痴呆症患者和非痴呆症对照组的死后海马切片进行染色、通过将 TDP-43 和 pTDP-43 与星形胶质细胞标记物胶质纤维酸性蛋白(GFAP)、星形胶质细胞内膜标记物 Aquaporin-4 (AQP4)、BBB 改变标记物(CD146)和渗漏标记物(免疫球蛋白 A)进行对比,我们发现血管周围 pTDP-43 或 TDP-43 包涵体与 GFAP 或 AQP4 密切相关。这些血管周围包涵物在 AD 中更为突出,并与疾病的严重程度以及 CD146 和 AQP4 的丧失相关。研究结果表明,pTDP-43在星形胶质细胞内膜的积聚与BBB和淋巴系统功能障碍之间存在关系,这可能是导致AD患者出现下游病理事件和病情恶化的原因之一。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Perivascular phosphorylated TDP-43 inclusions are associated with Alzheimer's disease pathology and loss of CD146 and Aquaporin-4

Perivascular phosphorylated TDP-43 inclusions are associated with Alzheimer's disease pathology and loss of CD146 and Aquaporin-4
The majority of patients with Alzheimer's disease (AD) exhibit aggregates of Trans-active response DNA binding protein 43 (TDP-43) in their hippocampus, which is associated with a more aggressive disease progression. The TDP-43 inclusions are commonly found in neurons, but also in astrocytes. The impact of the inclusions in astrocytes is less known. In the current study, we investigate the presence of phosphorylated TDP-43 (pTDP-43) inclusions in astrocytic endfeet and their potential association with blood–brain barrier (BBB) damage, glymphatic system dysfunction, and AD pathology. By staining postmortem hippocampal sections from AD patients and non-demented controls against TDP-43 and pTDP-43 together with the astrocytic markers glial fibrillary acidic protein (GFAP), astrocytic endfeet marker Aquaporin-4 (AQP4), and markers for BBB alterations (CD146) and leakiness (Immunoglobulin A), we demonstrate a close association between perivascular pTDP-43 or TDP-43 inclusions and GFAP or AQP4. These perivascular inclusions were more prominent in AD and correlated with the disease severity and loss of CD146 and AQP4. The findings indicate a relationship between pTDP-43 accumulation in astrocytic endfeet and BBB and glymphatic system dysfunction, which may contribute to the downstream pathological events seen in AD patients and the aggressive disease progression.
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来源期刊
Brain Pathology
Brain Pathology 医学-病理学
CiteScore
13.20
自引率
3.10%
发文量
90
审稿时长
6-12 weeks
期刊介绍: Brain Pathology is the journal of choice for biomedical scientists investigating diseases of the nervous system. The official journal of the International Society of Neuropathology, Brain Pathology is a peer-reviewed quarterly publication that includes original research, review articles and symposia focuses on the pathogenesis of neurological disease.
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