title: Amyloid plaques dissociate pentameric to monomeric C-reactive protein: a novel pathomechanism driving cortical inflammation in Alzheimer's disease?
abstract: Beta-amyloid (Aβ) 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 Aβ 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 Aβ plaques generated in vitro and with non-aggregated Aβ(42) peptide. pCRP dissociation to mCRP was found only when co-incubated with Aβ 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 Aβ 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 Aβ plaques is relevant in Alzheimer pathobiology; potentially localizing and amplifying inflammation via the strong pro-inflammatory effects of locally generated mCRP.
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Frederik
authors.initials: F
authors.lastname: Strang
authors.forename: Amelie
authors.initials: A
authors.lastname: Scheichl
authors.forename: Yung-Chih
authors.initials: YC
authors.lastname: Chen
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.forename: Nay-Min
authors.initials: NM
authors.lastname: Htun
authors.forename: Nicole
authors.initials: N
authors.lastname: Bassler
authors.forename: Steffen U
authors.initials: SU
authors.lastname: Eisenhardt
authors.forename: Jonathon
authors.initials: J
authors.lastname: Habersberger
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002097:C-Reactive Protein / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology
chemical_list: D002097:C-Reactive Protein