{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:17:53Z","timestamp":1791497873087,"version":"4.3.4"},"reference-count":58,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Background: Alzheimer\u2019s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-\u03b2 (A\u03b2) plaques, neurofibrillary tangles, and progressive cognitive decline. Recent evidence has highlighted the role of blood\u2013brain barrier (BBB) dysfunction in the early stages of AD pathology. Objective: We sought to explore the histological structure and physiological function of the blood\u2013brain barrier, and to identify the shared pathological mechanisms between BBB disruption and Alzheimer\u2019s disease progression. Methods: This narrative review was conducted through a comprehensive search of peer-reviewed literature from 1997 to 2024, using databases such as PubMed, Elsevier, Scopus, and Google Scholar. Results: Multiple histological and cellular components\u2014including endothelial cells, pericytes, astrocytes, and tight junctions\u2014contribute to BBB integrity. The breakdown of this barrier in AD is associated with chronic inflammation, oxidative stress, vascular injury, pericyte degeneration, astrocyte polarity loss, and dysfunction of nutrient transport systems like Glucose Transporter Type 1 (GLUT1). These alterations promote neuroinflammation, amyloid-\u03b2 (A\u03b2) accumulation, and progressive neuronal damage. Conclusions: BBB dysfunction is not merely a consequence of AD but may act as an early and active driver of its pathogenesis. Understanding the mechanisms of BBB breakdown can lead to early diagnostic markers and novel therapeutic strategies aimed at preserving or restoring barrier integrity in Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/neurolint17100166","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T07:56:29Z","timestamp":1759996589000},"page":"166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Histological and Functional Breakdown of the Blood\u2212Brain Barrier in Alzheimer\u2019s Disease: A Multifactorial Intersection"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8442-0442","authenticated-orcid":false,"given":"Jordana Mariane","family":"Neyra Chauca","sequence":"first","affiliation":[{"name":"Facultad de Medicina, Universidad Aut\u00f3noma de Guadalajara, Guadalajara 45129, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graciela Gaddy","family":"Robles Martinez","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad Aut\u00f3noma de Guadalajara, Guadalajara 45129, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/ni.3102","article-title":"Innate immunity in Alzheimer\u2019s disease","volume":"16","author":"Heneka","year":"2015","journal-title":"Nat. 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