Michael Smith Laboratories, The University of British Columbia, 301-2185 East Mall, Vancouver, BC V6T 1Z4, Canada ; Department of Microbiology and Immunology, University of British Columbia, 1365-2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada ; The Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada ; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada ; Department of Zoology, University of British Columbia, 2370-6270 University Blvd, Vancouver, BC V6T 1Z4, Canada ; Department of Medical Genetics, 1364-2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA ; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Alzheimers Res Ther. 2013 Dec 19;5(6):64. doi: 10.1186/alzrt230. eCollection 2013.
Growing evidence suggests that vascular perturbation plays a critical role in the pathogenesis of Alzheimer's disease (AD). It appears to be a common feature in addition to the classic pathological hallmarks of amyloid beta (Aβ) plaques and neurofibrillary. Moreover, the accumulation of Aβ in the cerebral vasculature is closely associated with cognitive decline, and disruption of the blood-brain barrier (BBB) has been shown to coincide with the onset of cognitive impairment. Although it was originally hypothesized that the accumulation of Aβ and the subsequent disruption of the BBB were due to the impaired clearance of Aβ from the brain, a body of data now suggests an alternative hypothesis for vascular dysfunction in AD that amyloidogenesis promotes extensive neoangiogenesis leading to increased vascular permeability and subsequent hypervascularization. In this review, we discuss the role Aβ plays in angiogenesis of the neurovasculature and BBB and how it may contribute to the pathogenesis of AD. These studies suggest that interventions that directly or indirectly affect angiogenesis could have beneficial effects on amyloid and other pathways in AD.
越来越多的证据表明，血管功能紊乱在阿尔茨海默病（AD）的发病机制中起着关键作用。除了淀粉样β（Aβ）斑块和神经原纤维缠结等经典病理学特征外，它似乎是一种常见特征。此外，Aβ在脑血管中的积累与认知能力下降密切相关，而且血脑屏障（BBB）的破坏与认知障碍的发生同时发生。尽管最初假设 Aβ的积累以及随后的 BBB 破坏是由于 Aβ从大脑中的清除受损所致，但现在有大量数据表明 AD 中血管功能障碍的另一种假设，即淀粉样蛋白生成促进广泛的新血管生成，导致血管通透性增加，随后发生过度血管化。在这篇综述中，我们讨论了 Aβ在神经血管和 BBB 的血管生成中的作用，以及它如何可能导致 AD 的发病机制。这些研究表明，直接或间接影响血管生成的干预措施可能对 AD 中的淀粉样蛋白和其他途径产生有益影响。
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