Occludin deficiency with BACE1 elevation in cerebral amyloid angiopathy.
Neurology
; 82(19): 1707-15, 2014 May 13.
Article
en En
| MEDLINE
| ID: mdl-24739782
ABSTRACT
OBJECTIVE:
A significant cause of spontaneous hemorrhages in the elderly is cerebral amyloid angiopathy (CAA), which causes degeneration of cerebral vessels, but the mechanisms are unclear.METHODS:
We isolated leptomeningeal vessels from rapidly autopsied brains (the average of postmortem intervals was 3.28 hours) from 9 patients with CAA and 10 age-matched controls, and used molecular, cell biology, and immunohistochemical approaches to examine ß-site APP-cleaving enzyme 1 (BACE1) protein expression and enzymatic activities as well as tight junction molecular components in small- and medium-sized arteries of the cerebral cortex and leptomeninges.RESULTS:
We not only identified that the cerebral vessels, including leptomeningeal and cortical vessels, synthesize and express BACE1, but also found a significant elevation of both BACE1 protein levels and enzymatic activities in leptomeningeal vessels from patients with CAA. Moreover, overexpression of BACE1 in endothelial cells resulted in a significant reduction of occludin, a tight junction protein in blood vessels.CONCLUSION:
These findings suggest that in addition to neurons, cerebral vascular cells express functional BACE1. Moreover, elevated vascular BACE1 may contribute to deficiency of occludin in cerebral vessels, which ultimately has a critical role in pathogenesis of CAA and its related hemorrhage.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ácido Aspártico Endopeptidasas
/
Angiopatía Amiloide Cerebral
/
Secretasas de la Proteína Precursora del Amiloide
/
Ocludina
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Límite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Neurology
Año:
2014
Tipo del documento:
Article