{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:29:36Z","timestamp":1792045776020,"version":"4.4.0"},"reference-count":216,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T00:00:00Z","timestamp":1635292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS104127"],"award-info":[{"award-number":["R01NS104127"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG062572"],"award-info":[{"award-number":["R01AG062572"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Edward N. and Della L. Thome Memorial Foundation Award in Alzheimer\u2019s Disease Drug Discovery Research","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Pennsylvania Department of Heath Collaborative Research on Alzheimer\u2019s Disease","award":["4100087336"],"award-info":[{"award-number":["4100087336"]}]},{"name":"the Karen Toffler Charitable Trust","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Lemole Center for Integrated Lymphatics research","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most prevalent cause of dementia and is pathologically characterized by the presence of parenchymal senile plaques composed of amyloid \u03b2 (A\u03b2) and intraneuronal neurofibrillary tangles of hyperphosphorylated tau protein. The accumulation of A\u03b2 also occurs within the cerebral vasculature in over 80% of AD patients and in non-demented individuals, a condition called cerebral amyloid angiopathy (CAA). The development of CAA is associated with neurovascular dysfunction, blood\u2013brain barrier (BBB) leakage, and persistent vascular- and neuro-inflammation, eventually leading to neurodegeneration. Although pathologically AD and CAA are well characterized diseases, the chronology of molecular changes that lead to their development is still unclear. Substantial evidence demonstrates defects in mitochondrial function in various cells of the neurovascular unit as well as in the brain parenchyma during the early stages of AD and CAA. Dysfunctional mitochondria release danger-associated molecular patterns (DAMPs) that activate a wide range of inflammatory pathways. In this review, we gather evidence to postulate a crucial role of the mitochondria, specifically of cerebral endothelial cells, as sensors and initiators of A\u03b2-induced vascular inflammation. The activated vasculature recruits circulating immune cells into the brain parenchyma, leading to the development of neuroinflammation and neurodegeneration in AD and CAA.<\/jats:p>","DOI":"10.3390\/cells10112903","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T22:00:23Z","timestamp":1635372023000},"page":"2903","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Dissecting the Crosstalk between Endothelial Mitochondrial Damage, Vascular Inflammation, and Neurodegeneration in Cerebral Amyloid Angiopathy and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0466-1047","authenticated-orcid":false,"given":"Rebecca M.","family":"Parodi-Rull\u00e1n","sequence":"first","affiliation":[{"name":"Alzheimer\u2019s Center at Temple, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7024-5383","authenticated-orcid":false,"given":"Sabzali","family":"Javadov","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Puerto Rico School of Medicine, San Juan, PR 00921, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2047-222X","authenticated-orcid":false,"given":"Silvia","family":"Fossati","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Center at Temple, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2021). 2021 Alzheimer\u2019s disease facts and figures. 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