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By regulating vascular functions and inflammation in the microvasculature, a disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS13) plays a significant protective effect in atherosclerosis and stroke. However, whether ADAMTS13 influences AD pathogenesis remains unclear. Using in vivo multiphoton microscopy, histological, behavioral, and biological methods, we determined BBB integrity, cerebrovascular dysfunction, amyloid accumulation, and cognitive impairment in <jats:italic>APPPS1<\/jats:italic> mice lacking ADAMTS13. We also tested the impact of viral-mediated expression of ADAMTS13 on cerebrovascular function and AD-like pathology in <jats:italic>APPPS1<\/jats:italic> mice. We show that ADAMTS13 deficiency led to an early and progressive BBB breakdown as well as reductions in vessel density, capillary perfusion, and cerebral blood flow in <jats:italic>APPPS1<\/jats:italic> mice. We found that deficiency of ADAMTS13 increased brain plaque load and A\u03b2 levels and accelerated cerebral amyloid angiopathy (CAA) by impeding BBB-mediated clearance of brain A\u03b2, resulting in worse cognitive decline in <jats:italic>APPPS1<\/jats:italic> mice. Virus-mediated expression of ADAMTS13 attenuated BBB disruption and increased microvessels, capillary perfusion, and cerebral blood flow in <jats:italic>APPPS1<\/jats:italic> mice already showing BBB damage and plaque deposition. These beneficial vascular effects were reflected by increase in clearance of cerebral A\u03b2, reductions in A\u03b2 brain accumulation, and improvements in cognitive performance. Our results show that ADAMTS13 deficiency contributes to AD cerebrovascular dysfunction and the resulting pathogenesis and cognitive deficits and suggest that ADAMTS13 may offer novel therapeutic opportunities for AD.<\/jats:p>","DOI":"10.1371\/journal.pbio.3000313","type":"journal-article","created":{"date-parts":[[2019,6,11]],"date-time":"2019-06-11T17:23:37Z","timestamp":1560273817000},"page":"e3000313","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":30,"title":["ADAMTS13 maintains cerebrovascular integrity to ameliorate Alzheimer-like 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