Open AccessA Shift in Microglial β‐Amyloid Binding in A lzheimer's Disease Is Associated with Cerebral Amyloid Angiopathy
Author(s) -
Zabel Matthew,
Schrag Matthew,
Crofton Andrew,
Tung Spencer,
Beaufond Pierre,
Van Ornam Jon,
DiNinni Angielee,
Vinters Harry V.,
Coppola Giovanni,
Kirsch Wolff M.
Publication year - 2013
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12005
Subject(s) - cerebral amyloid angiopathy , integrin alpha m , pathology , microglia , senile plaques , alzheimer's disease , parenchyma , complement membrane attack complex , complement system , chemistry , biology , receptor , immunology , medicine , inflammation , antibody , biochemistry , disease , dementia
Alzheimer's disease ( AD ) and cerebral amyloid angiopathy ( CAA ) are two common pathologies associated with β‐amyloid ( A β) 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 A β ligands thought to mediate A β 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 C 3b, membrane attack complex ( MAC ), CD 11b and α‐2‐macroglobulin and immunoprecipitation was used to immunoprecipitate ( IP ) CD 11b complexed with C 3b and A β. Both C 3b and MAC were significantly increased in CAA compared to AD ‐only and controls and IP showed significantly increased CD11b/C3b complexes with A β 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 A β clearance mechanism via microglial CD 11b that delivers A β and C 3b to blood vessels in AD / CAA , which leads to A β deposition and propagation of complement to the cytolytic MAC , possibly leading to vascular fragility.