Age-Stratified Analysis of Blood-Brain Barrier Proteins Identifies Lower Occludin Abundance in the 3xTg-AD Model.
4 affiliations
- 1Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México C.P. 07360, Mexico.
- 2Laboratorio de Investigación en Neurociencias, Envejecimiento y Neurodegeneración (LINEN), Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Ciudad de México C.P. 54090, Mexico.
- 3Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro C.P. 76230, Mexico.
- 4Programa de Posgrado en Ciencias Biológicas, Unidad de Posgrado, Edificio A, Primer Piso, Circuito de Posgrado, Ciudad Universitaria, Coyoacán, Ciudad de México C.P. 04510, Mexico.
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which blood-brain 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 3-5 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.
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BibTeX
@article{delgadominjares2026agestratified,
title = {{Age-Stratified Analysis of Blood-Brain Barrier Proteins Identifies Lower Occludin Abundance in the 3xTg-AD Model.}},
author = {Karen Michelle Delgado-Minjares and Catalina Flores-Maldonado and Jessica Paulina Campos-Blázquez and Sofía Y Díaz-Miranda and Jesús Andrade-Guerrero and Wendolin Colín-García and Karen León-Arcia and Daniel Martinez-Fong and Rubén G Contreras and Luis O Soto-Rojas},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198705},
url = {https://europepmc.org/article/MED/42883949},
note = {CC BY},
}
RIS
TY - JOUR
TI - Age-Stratified Analysis of Blood-Brain Barrier Proteins Identifies Lower Occludin Abundance in the 3xTg-AD Model.
AU - Karen Michelle Delgado-Minjares
AU - Catalina Flores-Maldonado
AU - Jessica Paulina Campos-Blázquez
AU - Sofía Y Díaz-Miranda
AU - Jesús Andrade-Guerrero
AU - Wendolin Colín-García
AU - Karen León-Arcia
AU - Daniel Martinez-Fong
AU - Rubén G Contreras
AU - Luis O Soto-Rojas
PY - 2026
DA - 2026/09/29
JO - International journal of molecular sciences
DO - 10.3390/ijms27198705
UR - https://europepmc.org/article/MED/42883949
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which blood-brain 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 3-5 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.
SN - 1422-0067
ER -