Vascular-Apoptotic Crosstalk in Alzheimer's Disease: The Possible Role of Vascular Senescence in Blood-Brain Barrier Dysfunction.

Authors

Carlangelo Carrese, Chiara Giuseppina Bonomi, Francesca Bernocchi, Martina Gaia Di Donna, Martina Poli, Guido Greco, Nicola Biagio Mercuri, Alessandro Martorana, Caterina Motta

Published in

European journal of neurology. Volume 33. Issue 7. Pages e70679.

Abstract

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.
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.
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.
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.

PMID:
42444286
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.