Document Detail

A shift in microglial β-amyloid binding in Alzheimer's disease is associated with cerebral amyloid angiopathy.
MedLine Citation:
PMID:  23134465     Owner:  NLM     Status:  MEDLINE    
Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) are two common pathologies associated with β-amyloid (Aβ) accumulation and inflammation in the brain; neither is well understood. The objective of this study was to evaluate human post-mortem brains from AD subjects with purely parenchymal pathology, and those with concomitant CAA (and age-matched controls) for differential expression of microglia-associated Aβ ligands thought to mediate Aβ clearance and the association of these receptors with complement activation. Homogenates of brain parenchyma and enriched microvessel fractions from occipital cortex were probed for levels of C3b, membrane attack complex (MAC), CD11b and α-2-macroglobulin and immunoprecipitation was used to immunoprecipitate (IP) CD11b complexed with C3b and Aβ. Both C3b and MAC were significantly increased in CAA compared to AD-only and controls and IP showed significantly increased CD11b/C3b complexes with Aβ in AD/CAA subjects. Confocal microscopy was used to visualize these interactions. MAC was remarkably associated with CAA-affected blood vessels compared to AD-only and control vessels. These findings are consistent with an Aβ clearance mechanism via microglial CD11b that delivers Aβ and C3b to blood vessels in AD/CAA, which leads to Aβ deposition and propagation of complement to the cytolytic MAC, possibly leading to vascular fragility.
Matthew Zabel; Matthew Schrag; Andrew Crofton; Spencer Tung; Pierre Beaufond; Jon Van Ornam; Angie Dininni; Harry V Vinters; Giovanni Coppola; Wolff M Kirsch
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-11-28
Journal Detail:
Title:  Brain pathology (Zurich, Switzerland)     Volume:  23     ISSN:  1750-3639     ISO Abbreviation:  Brain Pathol.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-18     Completed Date:  2014-01-27     Revised Date:  2014-07-02    
Medline Journal Info:
Nlm Unique ID:  9216781     Medline TA:  Brain Pathol     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  390-401     Citation Subset:  IM    
Copyright Information:
© 2012 International Society of Neuropathology.
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MeSH Terms
Actins / metabolism
Aged, 80 and over
Alzheimer Disease / complications,  genetics,  pathology*
Amyloid / metabolism*
Amyloid beta-Peptides / metabolism
Analysis of Variance
Antigens, CD / metabolism
Antigens, CD11b
Brain / metabolism,  pathology*
Cerebral Amyloid Angiopathy / complications*,  genetics,  pathology*
Complement Membrane Attack Complex / metabolism
Microglia / metabolism*
Microvessels / metabolism,  pathology
Middle Aged
Peptide Fragments / metabolism
Receptors, Complement / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/Actins; 0/Amyloid; 0/Amyloid beta-Peptides; 0/Antigens, CD; 0/Antigens, CD11b; 0/Complement Membrane Attack Complex; 0/Peptide Fragments; 0/Receptors, Complement; 0/amyloid beta-protein (1-40)

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