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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disorder in which blood\u2013brain barrier (BBB) dysfunction may arise early. We performed an age-stratified, cross-sectional analysis of pericyte- and endothelial-associated markers and junctional proteins (claudin-1, -3, -5, occludin, and VE-cadherin) in cerebral capillary-enriched fractions from male Non-Tg and 3xTg-AD mice at asymptomatic, early, and advanced stages (3, 6, 12, and 16 months of age). Protein abundance was assessed by Western blot, and BBB permeability to 3\u20135 kDa FITC-dextran was evaluated at 3 months in an independent cohort. At 3 months, the pSRC\/SRC ratio and an MMP-9-immunoreactive band were also evaluated in a separate cohort as candidate signaling markers related to occludin dysregulation. We detected no significant age or genotype effects for the pericyte- and endothelial-associated markers or for most junctional protein outcomes. Occludin was the only protein outcome with a significant overall genotype effect, with the largest mean reductions observed at 3 (~80%) and 6 months (~68%). A small exploratory cohort showed a higher hemisphere-derived permeability index in 3xTg-AD mice at 3 months. Neither pSRC\/SRC nor the abundance of the MMP-9-immunoreactive band differed significantly between genotypes. These findings identify lower occludin abundance as the principal BBB-associated protein alteration in the 3xTg-AD model and provide exploratory evidence of increased BBB permeability at 3 months. These independent observations warrant longitudinal and translational evaluation to determine whether occludin abundance and BBB permeability could serve as indicators of early neurovascular dysfunction in AD.<\/jats:p>","DOI":"10.3390\/ijms27198705","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:09:25Z","timestamp":1790683765000},"page":"8705","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age-Stratified Analysis of Blood\u2013Brain Barrier Proteins Identifies Lower Occludin Abundance in the 3xTg-AD Model"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8321-0705","authenticated-orcid":false,"given":"Karen Michelle","family":"Delgado-Minjares","sequence":"first","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Biof\u00edsica y Neurociencias, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto 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