{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T01:48:39Z","timestamp":1793843319082,"version":"4.6.1"},"reference-count":236,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:00:00Z","timestamp":1613606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most common neurodegenerative disease worldwide. Histopathologically, AD presents with two hallmarks: neurofibrillary tangles (NFTs), and aggregates of amyloid \u03b2 peptide (A\u03b2) both in the brain parenchyma as neuritic plaques, and around blood vessels as cerebral amyloid angiopathy (CAA). According to the vascular hypothesis of AD, vascular risk factors can result in dysregulation of the neurovascular unit (NVU) and hypoxia. Hypoxia may reduce A\u03b2 clearance from the brain and increase its production, leading to both parenchymal and vascular accumulation of A\u03b2. An increase in A\u03b2 amplifies neuronal dysfunction, NFT formation, and accelerates neurodegeneration, resulting in dementia. In recent decades, therapeutic approaches have attempted to decrease the levels of abnormal A\u03b2 or tau levels in the AD brain. However, several of these approaches have either been associated with an inappropriate immune response triggering inflammation, or have failed to improve cognition. Here, we review the pathogenesis and potential therapeutic targets associated with dysfunction of the NVU in AD.<\/jats:p>","DOI":"10.3390\/ijms22042022","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T20:56:21Z","timestamp":1613681781000},"page":"2022","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":136,"title":["The Neurovascular Unit Dysfunction in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5013-3608","authenticated-orcid":false,"given":"Luis O.","family":"Soto-Rojas","sequence":"first","affiliation":[{"name":"Facultad de Estudios Superiores Iztacala, UNAM, Mexico City 54090, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1983-0608","authenticated-orcid":false,"given":"Mar","family":"Pacheco-Herrero","sequence":"additional","affiliation":[{"name":"Neuroscience Research Laboratory, Faculty of Health Sciences, Pontificia Universidad Catolica Madre y Maestra, Santiago de los Caballeros 51000, Dominican Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8786-2911","authenticated-orcid":false,"given":"Paola A.","family":"Mart\u00ednez-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Facultad de Estudios Superiores Iztacala, UNAM, Mexico City 54090, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2426-9229","authenticated-orcid":false,"given":"B. Berenice","family":"Campa-C\u00f3rdoba","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 07738, Mexico"},{"name":"National Dementia BioBank, Ciencias Biol\u00f3gicas, Facultad de Estudios Superiores, Cuautitl\u00e1n, UNAM, Mexico City 53150, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Ap\u00e1tiga-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 07738, Mexico"},{"name":"National Dementia BioBank, Ciencias Biol\u00f3gicas, Facultad de Estudios Superiores, Cuautitl\u00e1n, UNAM, Mexico City 53150, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos M.","family":"Villegas-Rojas","sequence":"additional","affiliation":[{"name":"Unidad Profesional Interdisciplinaria de Biotecnolog\u00eda del Instituto Polit\u00e9cnico Nacional (UPIBI-IPN), Mexico City 07340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Harrington","sequence":"additional","affiliation":[{"name":"School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fidel","family":"de la Cruz","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 07738, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Garc\u00e9s-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 07738, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Luna-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"National Dementia BioBank, Ciencias Biol\u00f3gicas, Facultad de Estudios Superiores, Cuautitl\u00e1n, UNAM, Mexico City 53150, Mexico"},{"name":"Banco Nacional de Cerebros-UNPHU, Universidad Nacional Pedro Henr\u00edquez Ure\u00f1a, Santo Domingo 2796, Dominican Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,18]]},"reference":[{"key":"ref_1","first-page":"27","article-title":"Astrocytes function in matching blood flow to metabolic activity","volume":"17","author":"Harder","year":"2002","journal-title":"News Physiol. 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