Facultad de Estudios Superiores Iztacala, UNAM, Mexico City 54090, Mexico.
Neuroscience Research Laboratory, Faculty of Health Sciences, Pontificia Universidad Catolica Madre y Maestra, Santiago de los Caballeros 51000, Dominican Republic.
Int J Mol Sci. 2021 Feb 18;22(4):2022. doi: 10.3390/ijms22042022.
Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide. Histopathologically, AD presents with two hallmarks: neurofibrillary tangles (NFTs), and aggregates of amyloid β peptide (Aβ) both in the brain parenchyma as neuritic plaques, and around blood vessels as cerebral amyloid angiopathy (CAA). According to the vascular hypothesis of AD, vascular risk factors can result in dysregulation of the neurovascular unit (NVU) and hypoxia. Hypoxia may reduce Aβ clearance from the brain and increase its production, leading to both parenchymal and vascular accumulation of Aβ. An increase in Aβ amplifies neuronal dysfunction, NFT formation, and accelerates neurodegeneration, resulting in dementia. In recent decades, therapeutic approaches have attempted to decrease the levels of abnormal Aβ or tau levels in the AD brain. However, several of these approaches have either been associated with an inappropriate immune response triggering inflammation, or have failed to improve cognition. Here, we review the pathogenesis and potential therapeutic targets associated with dysfunction of the NVU in AD.
阿尔茨海默病（AD）是全球最常见的神经退行性疾病。组织病理学上，AD 有两个特征性表现：神经纤维缠结（NFTs）和淀粉样 β 肽（Aβ）聚集物，既存在于脑实质中的神经原纤维缠结，也存在于血管周围的脑淀粉样血管病（CAA）中。根据 AD 的血管假说，血管危险因素可导致神经血管单元（NVU）失调和缺氧。缺氧可能会降低脑内 Aβ 的清除率并增加其生成，从而导致 Aβ 在脑实质和血管中的积累。Aβ 的增加会放大神经元功能障碍、NFT 形成，并加速神经退行性变，导致痴呆。近几十年来，治疗方法试图降低 AD 脑中异常 Aβ 或 tau 水平。然而，其中一些方法要么与不适当的免疫反应引发炎症有关，要么未能改善认知。在这里，我们综述了与 AD 中 NVU 功能障碍相关的发病机制和潜在治疗靶点。
