"Morphological, Functional, and Molecular Progression of Blood-Brain Barrier Dysfunction in Alzheimer's Disease".
6 affiliations
- 1Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, 76230, México.
- 2Laboratorio de Investigación en Neurociencias, Envejecimiento y Neurodegeneración (LINEN), Facultad de Estudios Superiores de Iztacala, UNAM, Tlalnepantla de Baz, 54090, México.
- 3PhD Student, Posgrado en Ciencias Biológicas, Unidad de Posgrado, UNAM, Edificio A, 1er Piso, Circuito de Posgrado, Ciudad Universitaria, Ciudad de México, 04510, México.
- 4Laboratorio de Medicina Regenerativa, Departamento de Fisiología, Facultad de Medicina, UNAM, Ciudad de México, 04510, México.
- 5Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, 76230, México. [email protected].
- 6Laboratorio de Investigación en Neurociencias, Envejecimiento y Neurodegeneración (LINEN), Facultad de Estudios Superiores de Iztacala, UNAM, Tlalnepantla de Baz, 54090, México. [email protected].
Abstract
Blood-brain barrier (BBB) dysfunction is increasingly recognized as an early pathological event in sporadic Alzheimer's disease (AD), which represents over 95% of cases. Vascular risk factors and cerebral insulin resistance are considered potential contributors to its initiation. This review synthesizes evidence available through March 2026 on the temporal progression of morphological, functional, and molecular BBB alterations in AD patients and experimental models. This review emphasizes the proposed role of BBB disruption in perpetuating neurodegeneration through feedback loops involving pericyte damage, hypoxia, perivascular inflammation, and dysregulation of amyloid-β transport systems. By integrating data from neuroimaging, fluid biomarkers, and post-mortem studies, available evidence suggests that BBB alterations can be detected from preclinical stages, most consistently in the hippocampus, and may exhibit sex-specific differences. The review compares findings from familial transgenic models with the more limited characterization available in sporadic AD models (notably the intracerebroventricular streptozotocin model), and highlights key knowledge gaps regarding temporal dynamics. This synthesis supports further exploration of strategies to preserve BBB integrity. An integrated vascular approach may usefully complement current amyloid- and tau-centered therapies, particularly in sporadic AD.
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BibTeX
@article{leonarcia2026morphological,
title = {{"Morphological, Functional, and Molecular Progression of Blood-Brain Barrier Dysfunction in Alzheimer's Disease".}},
author = {Karen León-Arcia and Humberto Martínez-Orozco and Magdalena Guerra-Crespo and Sofía Y Díaz-Miranda and Luis O Soto-Rojas},
journal = {Journal of molecular neuroscience : MN},
year = {2026},
month = oct,
doi = {10.1007/s12031-026-02610-0},
url = {https://europepmc.org/article/MED/42873408},
note = {CC BY},
}
RIS
TY - JOUR
TI - "Morphological, Functional, and Molecular Progression of Blood-Brain Barrier Dysfunction in Alzheimer's Disease".
AU - Karen León-Arcia
AU - Humberto Martínez-Orozco
AU - Magdalena Guerra-Crespo
AU - Sofía Y Díaz-Miranda
AU - Luis O Soto-Rojas
PY - 2026
DA - 2026/10/14
JO - Journal of molecular neuroscience : MN
DO - 10.1007/s12031-026-02610-0
UR - https://europepmc.org/article/MED/42873408
AB - Blood-brain barrier (BBB) dysfunction is increasingly recognized as an early pathological event in sporadic Alzheimer's disease (AD), which represents over 95% of cases. Vascular risk factors and cerebral insulin resistance are considered potential contributors to its initiation. This review synthesizes evidence available through March 2026 on the temporal progression of morphological, functional, and molecular BBB alterations in AD patients and experimental models. This review emphasizes the proposed role of BBB disruption in perpetuating neurodegeneration through feedback loops involving pericyte damage, hypoxia, perivascular inflammation, and dysregulation of amyloid-β transport systems. By integrating data from neuroimaging, fluid biomarkers, and post-mortem studies, available evidence suggests that BBB alterations can be detected from preclinical stages, most consistently in the hippocampus, and may exhibit sex-specific differences. The review compares findings from familial transgenic models with the more limited characterization available in sporadic AD models (notably the intracerebroventricular streptozotocin model), and highlights key knowledge gaps regarding temporal dynamics. This synthesis supports further exploration of strategies to preserve BBB integrity. An integrated vascular approach may usefully complement current amyloid- and tau-centered therapies, particularly in sporadic AD.
SN - 0895-8696
SN - 1559-1166
ER -