Vascular-Apoptotic Crosstalk in Alzheimer's Disease: The Possible Role of Vascular Senescence in Blood-Brain Barrier Dysfunction.
C, C., CG, B., F, B., MGD, D., M, P., G, G., NB, M., A, M., & C, M. (2026). Vascular-Apoptotic Crosstalk in Alzheimer's Disease: The Possible Role of Vascular Senescence in Blood-Brain Barrier Dysfunction.. European journal of neurology. https://doi.org/10.1111/ene.70679
C C, CG B, F B, MGD D, M P, G G, et al. Vascular-Apoptotic Crosstalk in Alzheimer's Disease: The Possible Role of Vascular Senescence in Blood-Brain Barrier Dysfunction.. European journal of neurology. 2026; doi: 10.1111/ene.70679
C C, CG B, F B, et al. Vascular-Apoptotic Crosstalk in Alzheimer's Disease: The Possible Role of Vascular Senescence in Blood-Brain Barrier Dysfunction.[J]. European journal of neurology. 2026. DOI: 10.1111/ene.70679.
@article{c2026,
author = {Carrese C and Bonomi CG and Bernocchi F and Donna MGD and Poli M and Greco G and Mercuri NB and Martorana A and Motta C},
title = {Vascular-Apoptotic Crosstalk in Alzheimer's Disease: The Possible Role of Vascular Senescence in Blood-Brain Barrier Dysfunction.},
journal = {European journal of neurology},
year = {2026},
doi = {10.1111/ene.70679},
note = {PMID: 42444286},
}
TY - JOUR AU - Carrese C AU - Bonomi CG AU - Bernocchi F AU - Donna MGD AU - Poli M AU - Greco G AU - Mercuri NB AU - Martorana A AU - Motta C TI - Vascular-Apoptotic Crosstalk in Alzheimer's Disease: The Possible Role of Vascular Senescence in Blood-Brain Barrier Dysfunction. T2 - European journal of neurology PY - 2026 DO - 10.1111/ene.70679 AN - PMID:42444286 ER -
BACKGROUND: Blood-brain barrier (BBB) dysfunction is an early feature of Alzheimer's disease (AD), influenced by amyloid pathology, astrocyte activation, and vasoactive mediators such as endothelin-1 (ET-1). ET-1 has been implicated in apoptosis and vascular senescence through induction of p53, a pro-apoptotic factor, whereas BCL-X exerts antiapoptotic effects. We investigated the interplay between ET-1, p53, and BCL-X in AD and their contribution to BBB permeability. METHODS: We studied 101 individuals (70 AD, 31 controls) who underwent cerebrospinal fluid (CSF) analysis for Aβ42, p-tau, ET-1, p53, BCL-X, and the CSF/serum albumin quotient (QAlb), an index of BBB permeability. Correlations between biomarkers were explored, followed by multiple regression and mediation analysis to assess whether p53 mediated the ET-1-BBB relationship. RESULTS: No absolute differences in ET-1, p53, or BCL-X were found between AD and controls. However, in AD, ET-1 correlated positively with p53 and negatively with BCL-X, whereas no such associations were seen in controls. None of these biomarkers related to the p-tau/Aβ42 ratio. Regression analysis identified both ET-1 and p53 as independent predictors of BBB permeability. Mediation analysis further revealed that ET-1 influenced BBB permeability both directly and indirectly through p53. CONCLUSION: Our findings suggest that AD is characterized less by absolute biomarker changes and more by altered interrelationships linking ET-1, apoptosis, and BBB integrity. ET-1 may promote BBB dysfunction partly via p53, which is consistent with the mechanisms of vascular senescence. These results highlight apoptosis-vascular interactions as potential drivers of BBB impairment in AD.