From Stroke to Dementia: a Comprehensive Review Exposing Tight Interactions Between Stroke and Amyloid-β Formation

作者：Romain Goulay, Luis Mena Romo, Elly M. Hol, Rick M. Dijkhuizen · 发表于：Translational Stroke Research · 年份：2019 · DOI：10.1007/s12975-019-00755-2 · 被引用次数：141 · 研究领域：Intracerebral and Subarachnoid Hemorrhage Research、Cerebrospinal fluid and hydrocephalus、Alzheimer's disease research and treatments

Stroke and Alzheimer's disease (AD) are cerebral pathologies with high socioeconomic impact that can occur together and mutually interact. Vascular factors predisposing to cerebrovascular disease have also been specifically associated with development of AD, and acute stroke is known to increase the risk to develop dementia.Despite the apparent association, it remains unknown how acute cerebrovascular disease and development of AD are precisely linked and act on each other. It has been suggested that this interaction is strongly related to vascular deposition of amyloid-β (Aβ), i.e., cerebral amyloid angiopathy (CAA). Furthermore, the blood-brain barrier (BBB), perivascular space, and the glymphatic system, the latter proposedly responsible for the drainage of solutes from the brain parenchyma, may represent key pathophysiological pathways linking stroke, Aβ deposition, and dementia.In this review, we propose a hypothetic connection between CAA, stroke, perivascular space integrity, and dementia. Based on relevant pre-clinical research and a few clinical case reports, we speculate that impaired perivascular space integrity, inflammation, hypoxia, and BBB breakdown after stroke can lead to accelerated deposition of Aβ within brain parenchyma and cerebral vessel walls or exacerbation of CAA. The deposition of Aβ in the parenchyma would then be the initiating event leading to synaptic dysfunction, inducing cognitive decline and dementia. Maintaining the clearance of Aβ after str...