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Cerebral amyloid angiopathy is a form of cerebrovascular pathology that results from the build-up of \u03b2-amyloid in the vessel walls. Cerebral amyloid angiopathy commonly co-occurs with Alzheimer\u2019s disease pathology in the ageing brain and increases the risk of Alzheimer\u2019s disease dementia.<\/jats:p>\n                  <jats:p>In the present study, we examined whether cerebral amyloid angiopathy influences tau deposition and cognitive decline independently or synergistically with parenchymal \u03b2-amyloid burden. Secondly, we examined whether tau burden mediates the association between cerebral amyloid angiopathy and cognitive decline. We included data from autopsied subjects recruited from one of three longitudinal clinical\u2013pathological cohort studies: the Rush Memory and Aging Project, the Religious Orders Study and the Minority Aging Research Study. Participants completed annual clinical and cognitive evaluations and underwent brain autopsy. Cerebral amyloid angiopathy pathology was rated as none, mild, moderate or severe. Bielschowsky silver stain was used to visualize neuritic \u03b2-amyloid plaques and neurofibrillary tangles. We used linear regression and linear mixed models to test independent versus interactive associations of cerebral amyloid angiopathy and neuritic plaque burden with tau burden and longitudinal cognitive decline, respectively. We used causal mediation models to examine whether tau mediates the association between cerebral amyloid angiopathy and cognitive decline. The study sample included 1722 autopsied subjects (age at baseline\u2009=\u200980.2\u2009\u00b1\u20097.1 years; age at death\u2009=\u200989.5\u2009\u00b1\u20096.7 years; 68% females).<\/jats:p>\n                  <jats:p>Cerebral amyloid angiopathy interacted with neuritic plaques to accelerate tau burden and cognitive decline. Specifically, those with more severe cerebral amyloid angiopathy pathology and higher levels of neuritic plaque burden had greater tau burden and faster cognitive decline. We also found that tau mediated the association between cerebral amyloid angiopathy and cognitive decline among participants with higher neuritic plaque burden. In summary, more severe levels of cerebral amyloid angiopathy and higher parenchymal \u03b2-amyloid burden interacted to promote cognitive decline indirectly via tau deposition. These results highlight the dynamic interplay between cerebral amyloid angiopathy and Alzheimer\u2019s disease pathology in accelerating progression toward dementia. These findings have implications for Alzheimer\u2019s disease clinical trials and therapeutic development.<\/jats:p>","DOI":"10.1093\/brain\/awac178","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T11:42:12Z","timestamp":1656330132000},"page":"2823-2833","source":"Crossref","is-referenced-by-count":80,"title":["Cerebral amyloid angiopathy interacts with neuritic amyloid plaques to promote tau and cognitive decline"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4754-2221","authenticated-orcid":false,"given":"Jennifer S","family":"Rabin","sequence":"first","affiliation":[{"name":"Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto , Toronto , Canada M4N 3M5"},{"name":"Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Research Institute , Toronto, Ontario , Canada M4N 3M5"},{"name":"Rehabilitation Sciences Institute, University of Toronto , Toronto , Canada M5G 1V7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2581-8100","authenticated-orcid":false,"given":"Renaud","family":"La Joie","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California , San Francisco, CA , USA 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0610-6933","authenticated-orcid":false,"given":"Kaitlin B","family":"Casaletto","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California , San Francisco, CA , USA 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Palta","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Epidemiology, Columbia University Irving Medical Center , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Dams-O\u2019Connor","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai , New York, NY , USA 10029"},{"name":"Department of Neurology, Icahn School of Medicine at Mount Sinai , New York, NY , USA 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj G","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai , New York, NY , USA 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8773-7678","authenticated-orcid":false,"given":"Kristen M","family":"George","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of California Davis School of Medicine , Davis, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia L","family":"Satizabal","sequence":"additional","affiliation":[{"name":"Department of Population Health Science and Biggs Institute for Alzheimer\u2019s and Neurodegenerative Diseases, UT Health San Antonio , San Antonio, TX , USA"},{"name":"Department of Neurology, Boston University School of Medicine , Boston, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A","family":"Schneider","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center, Rush University Medical Center , Chicago, IL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Pa","sequence":"additional","affiliation":[{"name":"Mark and Mary Stevens Neuroimaging and Informatics Institute, Department of Neurology, University of Southern California , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5125-8226","authenticated-orcid":false,"given":"Adam M","family":"Brickman","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Department of Neurology, College of Physicians and Surgeons, Columbia University , New York, NY , USA 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"2022082719580238000_awac178-B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jalz.2011.10.007","article-title":"National Institute on 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