Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Neurobiol Aging. 2010 Sep;31(9):1569-81. doi: 10.1016/j.neurobiolaging.2008.08.017. Epub 2008 Oct 5.

Abeta accumulation in choroid plexus is associated with mitochondrial-induced apoptosis.

Author information

  • 1Neuroscience Laboratory, Research Center, Hospital 12 de Octubre, Madrid, Spain.

Abstract

One of the possible mechanisms involved in beta-amyloid (Abeta)-induced neuronal damage is blood-cerebrospinal fluid barrier dysfunction. Recently, we have demonstrated that Alzheimer patients have an elevated expression of Abeta in the choroid plexus (CP), where it could impair the physiological functions of CP epithelium. We investigated whether these alterations were mediated by mitochondrial dysfunction, a common early pathomechanism in Alzheimer's disease. Our main observations were: high Abeta levels; increased nitric oxide levels; impairment of the activity and assembly of mitochondrial respiratory chain complexes I and IV; and a significant increase in reactive oxygen species and caspase expression in CP epithelial cells treated with Abeta. Our results also demonstrate a direct relationship between Abeta toxicity, increased expression of matrix metalloproteinase-9, and blood-cerebrospinal fluid barrier disruption. We propose a sequence of pathological steps that link Abeta accumulation in CP epithelium with an enhanced nitric oxide production, mitochondrial dysfunction, and up-regulation of matrix metalloproteinase-9, which ultimately lead to cell death, and probably to CSF barrier dysfunction.

Copyright 2008 Elsevier Inc. All rights reserved.

PMID:
18838197
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk