Impact of Tau on Neurovascular Pathology in Alzheimer's Disease.
Impact of Tau on Neurovascular Pathology in Alzheimer's Disease.
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DOI：
10.3389/fneur.2020.573324
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发表时间：
2020
影响因子：
3.4
通讯作者：
Fossati S
中科院分区：
文献类型：
--
作者：
Canepa E;Fossati S
阿尔茨海默病（Alzheimer's disease，AD）是一种慢性神经退行性疾病，也是痴呆症最常见的病因。主要的脑组织学标志是淀粉样蛋白β（Aβ斑块）和神经纤维缠结（NFT）的实质不溶性沉积，tau（一种微管相关蛋白）的细胞内丝状包涵体。众所周知，脑血管功能障碍是AD病理学的早期特征，但导致血管损伤和相关神经血管失调的有害机制尚未完全了解。在90%的AD病例中，脑血管周围的Aβ沉积（称为脑淀粉样血管病（CAA））改变了血脑屏障（BBB）的基本功能。虽然血管Aβ蓄积的影响有更好的记录，但科学界最近才开始考虑tau对AD神经血管病理学的影响。新出现的令人信服的证据表明，神经元tau蛋白传递到不同的脑细胞，包括星形胶质细胞，以及释放到脑间质液中的tau蛋白，这可能导致血管周围神经原纤维tau蛋白积累和毒性，影响血管结构，脑血流量（CBF）和血管通透性。因此，BBB的完整性和功能性可能受到病理性tau的影响，从而加速疾病的进展。Tau聚集体也已显示诱导线粒体损伤：已知Tau损害线粒体定位、分布和动力学，改变ATP和活性氧物质产生，并损害氧化磷酸化系统。根据这些先前的知识，我们假设tau蛋白可以通过线粒体失调引发AD中的神经血管病理。在这篇综述中，我们将探讨研究tau病理学对脑血管和神经血管单位功能障碍的贡献，以及其与线粒体改变和半胱天冬酶激活的相关性，在AD和tau蛋白病的细胞，动物和人类研究中的文献。
Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most prevalent cause of dementia. The main cerebral histological hallmarks are represented by parenchymal insoluble deposits of amyloid beta (Aβ plaques) and neurofibrillary tangles (NFT), intracellular filamentous inclusions of tau, a microtubule-associated protein. It is well-established that cerebrovascular dysfunction is an early feature of AD pathology, but the detrimental mechanisms leading to blood vessel impairment and the associated neurovascular deregulation are not fully understood. In 90% of AD cases, Aβ deposition around the brain vasculature, known as cerebral amyloid angiopathy (CAA), alters blood brain barrier (BBB) essential functions. While the effects of vascular Aβ accumulation are better documented, the scientific community has only recently started to consider the impact of tau on neurovascular pathology in AD. Emerging compelling evidence points to transmission of neuronal tau to different brain cells, including astrocytes, as well as to the release of tau into brain interstitial fluids, which may lead to perivascular neurofibrillar tau accumulation and toxicity, affecting vessel architecture, cerebral blood flow (CBF), and vascular permeability. BBB integrity and functionality may therefore be impacted by pathological tau, consequentially accelerating the progression of the disease. Tau aggregates have also been shown to induce mitochondrial damage: it is known that tau impairs mitochondrial localization, distribution and dynamics, alters ATP and reactive oxygen species production, and compromises oxidative phosphorylation systems. In light of this previous knowledge, we postulate that tau can initiate neurovascular pathology in AD through mitochondrial dysregulation. In this review, we will explore the literature investigating tau pathology contribution to the malfunction of the brain vasculature and neurovascular unit, and its association with mitochondrial alterations and caspase activation, in cellular, animal, and human studies of AD and tauopathies.
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影响因子：
4.3
作者：
Bonora, Massimo;Bononi, Angela;Pinton, Paolo
通讯作者：
Pinton, Paolo
DOI：
10.1083/jcb.101.4.1371
发表时间：
1985-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Binder LI;Frankfurter A;Rebhun LI
通讯作者：
Rebhun LI
影响因子：
4.8
作者：
Avila J;Jiménez JS;Sayas CL;Bolós M;Zabala JC;Rivas G;Hernández F
通讯作者：
Hernández F
DOI：
10.1073/pnas.121119298
发表时间：
2001-06-05
影响因子：
11.1
作者：
Alonso, AD;Zaidi, T;Iqbal, K
通讯作者：
Iqbal, K
影响因子：
5
作者：
Bernardi, Paolo;Di Lisa, Fabio
通讯作者：
Di Lisa, Fabio