Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA.
Department of Pediatrics, University of California Irvine, Irvine, CA, USA.
J Cereb Blood Flow Metab. 2021 Aug;41(8):1821-1841. doi: 10.1177/0271678X21992462. Epub 2021 Feb 8.
Alzheimer's disease (AD) is a devastating neurological degenerative disorder and is the most common cause of dementia in the elderly. Clinically, AD manifests with memory and cognitive decline associated with deposition of hallmark amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs). Although the mechanisms underlying AD remains unclear, two hypotheses have been proposed. The established amyloid hypothesis states that Aβ accumulation is the basis of AD and leads to formation of NFTs. In contrast, the two-hit vascular hypothesis suggests that early vascular damage leads to increased accumulation of Aβ deposits in the brain. Multiple studies have reported significant morphological changes of the cerebrovasculature which can result in severe functional deficits. In this review, we delve into known structural and functional vascular alterations in various mouse models of AD and the cellular and molecular constituents that influence these changes to further disease progression. Many studies shed light on the direct impact of Aβ on the cerebrovasculature and how it is disrupted during the progression of AD. However, more research directed towards an improved understanding of how the cerebrovasculature is modified over the time course of AD is needed prior to developing future interventional strategies.
阿尔茨海默病（AD）是一种破坏性的神经退行性疾病，是老年人痴呆症的最常见原因。临床上，AD 表现为记忆和认知能力下降，同时伴有标志性的淀粉样β（Aβ）斑块和神经纤维缠结（NFTs）的沉积。尽管 AD 的发病机制尚不清楚，但已经提出了两种假说。已确立的淀粉样蛋白假说认为，Aβ的积累是 AD 的基础，并导致 NFT 的形成。相比之下，双重打击血管假说表明，早期的血管损伤会导致大脑中 Aβ沉积的增加。多项研究报告称，脑血管存在明显的形态学变化，这可能导致严重的功能缺陷。在这篇综述中，我们深入研究了各种 AD 小鼠模型中已知的血管结构和功能改变，以及影响这些变化从而进一步促进疾病进展的细胞和分子成分。许多研究都阐明了 Aβ对脑血管的直接影响，以及在 AD 进展过程中它是如何被破坏的。然而，在制定未来的干预策略之前，需要更多的研究来深入了解 AD 病程中脑血管是如何被改变的。
