Brain Vasculature Accumulates Tau and Is Spatially Related to Tau Tangle Pathology in Alzheimer's Disease.
Brain Vasculature Accumulates Tau and Is Spatially Related to Tau Tangle Pathology in Alzheimer's Disease.
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脑血管系统积累 Tau 蛋白并与阿尔茨海默病中的 Tau 蛋白缠结病理学在空间上相关。
DOI：
10.1101/2024.01.27.577088
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Bennett,RachelE
中科院分区：
文献类型：
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作者：
Hoglund,Zachary;Ruiz-Uribe,Nancy;DelSastre,Eric;Woost,Benjamin;Bailey,Joshua;Hyman,BradleyT;Zwang,Theodore;Bennett,RachelE
在脑淀粉样血管病（CAA）的情况下，不溶性致病蛋白质沿着血管沿着，对血管细胞产生毒性作用并影响脑内稳态。在这项工作中，我们提供了新的证据，从三维人脑组织学的tau蛋白，神经元缠结的主要成分，可以类似地积累沿着脑血管节段。我们定量评估了n = 6个阿尔茨海默病（AD）和n = 6个正常老化对照脑，并且看到在所有AD病例中存在tau阳性血管段。Tau阳性血管富含高于周围组织水平的Tau，并且似乎影响穿过皮质层的小动脉（I-V）。此外，从这些AD组织分离的血管富含N-末端tau和在T181和T217磷酸化的tau。重要的是，tau阳性血管与tau神经元缠结增加的局部区域相关。这表明tau在血管周围的积聚可能反映了局部清除失败。总而言之，这些数据表明tau与β淀粉样蛋白一样，沿着血管积聚，并可能对AD背景下的血管系统产生显着影响。
Insoluble pathogenic proteins accumulate along blood vessels in conditions of cerebral amyloid angiopathy (CAA), exerting a toxic effect on vascular cells and impacting cerebral homeostasis. In this work, we provide new evidence from three-dimensional human brain histology that tau protein, the main component of neurofibrillary tangles, can similarly accumulate along brain vascular segments. We quantitatively assessed n = 6 Alzheimer’s disease (AD), and n = 6 normal aging control brains and saw that tau-positive blood vessel segments were present in all AD cases. Tau-positive vessels are enriched for tau at levels higher than the surrounding tissue and appear to affect arterioles across cortical layers (I–V). Further, vessels isolated from these AD tissues were enriched for N-terminal tau and tau phosphorylated at T181 and T217. Importantly, tau-positive vessels are associated with local areas of increased tau neurofibrillary tangles. This suggests that accumulation of tau around blood vessels may reflect a local clearance failure. In sum, these data indicate that tau, like amyloid beta, accumulates along blood vessels and may exert a significant influence on vasculature in the setting of AD.