Amyloid plaques dissociate pentameric to monomeric C-reactive protein: a novel pathomechanism driving cortical inflammation in Alzheimer's disease?
Brain Pathol
; 22(3): 337-46, 2012 May.
Article
de En
| MEDLINE
| ID: mdl-21951392
ABSTRACT
Beta-amyloid (Aß) plaques and local inflammation are central to the pathogenesis of Alzheimer's disease. Although an association between circulating pentameric C-reactive protein (pCRP) and Alzheimer's disease has been reported no pathomechanistic link has been established. We hypothesized that Aß plaques induce the dissociation of pCRP to individual monomers (mCRP), which possess strong pro-inflammatory properties not shared with pCRP and localizing inflammation to Alzheimer's plaques. pCRP was incubated with Aß plaques generated in vitro and with non-aggregated Aß(42) peptide. pCRP dissociation to mCRP was found only when co-incubated with Aß plaques. Furthermore, sections of frontal cortex from brains of patients with and without Alzheimer's disease were stained with antibodies specific for mCRP and pCRP. There was significantly more mCRP in the cortex of Alzheimer's disease patients (P ≤ 0.01). In contrast, there was no significant difference in pCRP staining. These findings establish that Aß plaques possess a previously unrecognized potential to dissociate pentameric CRP to monomeric CRP. The existence of mCRP but not pCRP in the brains of Alzheimer's disease patients strongly indicates that this newly described biological effect of Aß plaques is relevant in Alzheimer pathobiology; potentially localizing and amplifying inflammation via the strong pro-inflammatory effects of locally generated mCRP.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Encéphale
/
Protéine C-réactive
/
Plaque amyloïde
/
Maladie d'Alzheimer
Limites:
Aged
/
Aged80
/
Female
/
Humans
/
Male
Langue:
En
Journal:
Brain Pathol
Sujet du journal:
CEREBRO
/
PATOLOGIA
Année:
2012
Type de document:
Article
Pays d'affiliation:
Australie