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However, the interplay among these pathologic changes of Alzheimer disease is not well understood. Here we replicate and extend findings of a recent study that suggested the association of cerebral amyloid angiopathy and cognitive impairment is mediated by neurofibrillary degeneration. We employed similar approaches but in a larger, clinical-based (as opposed to community-based) set of 4915 autopsied National Alzheimer\u2019s Coordinating Center participants (60% with dementia). Neuropathologic lesions were measured ordinally; longitudinal change in cognition was used to measure cognitive impairment. Statistical analyses included ordinal logistic regression, mediation analyses and extension of models to include presence of APOE e4. We show a statistical interaction between cerebral amyloid angiopathy and neuritic plaques that impacts the burden of neurofibrillary tangles. Mediation analyses show that cerebral amyloid angiopathy is associated with cognitive impairment, but only by modifying the impact of neurofibrillary tangles on cognition. We expanded the mediation analysis to include APOE e4 and show similar results. Findings indicate that cerebral amyloid angiopathy plays an important role in the burden and impact of neurofibrillary degeneration contributing to cognitive impairment.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae369","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T15:23:17Z","timestamp":1732116197000},"source":"Crossref","is-referenced-by-count":10,"title":["Cerebral amyloid angiopathy impacts neurofibrillary tangle burden and cognition"],"prefix":"10.1093","volume":"6","author":[{"given":"Dana","family":"Godrich","sequence":"first","affiliation":[{"name":"Dr. John T Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Pasteris","sequence":"additional","affiliation":[{"name":"Dr. John T Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami , Miami, FL 33136 ,","place":["USA"]},{"name":"John P. 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Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A","family":"Pericak-Vance","sequence":"additional","affiliation":[{"name":"Dr. John T Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami , Miami, FL 33136 ,","place":["USA"]},{"name":"John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L","family":"Cuccaro","sequence":"additional","affiliation":[{"name":"Dr. John T Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami , Miami, FL 33136 ,","place":["USA"]},{"name":"John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William K","family":"Scott","sequence":"additional","affiliation":[{"name":"Dr. John T Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami , Miami, FL 33136 ,","place":["USA"]},{"name":"John P. 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