Abstract Details

Title A Shift in Microglial ?-Amyloid Binding in Alzheimer's Disease Is Associated with Cerebral Amyloid Angiopathy

Topic Aging and Dementia

Presentation(s) P04 - (-)

Poster/Presentation
Number 216

Objective

Background BACKGROUND: Alzheimer disease (AD) is the most common neurodegenerative disease. Approximately 90% of AD cases also manifest a vasculopathy called cerebral amyloid angiopathy (CAA), characterized by amyloid beta (A?) deposition in the brain microvasculature. This deposition process and the resulting microbleeds are not yet fully understood.

Design/Methods DESIGN/METHODS: We used postmortem human brain specimens (control, AD only, and AD/CAA) and an enriched microvessel fraction from the occipital lobe for western blot analysis to measure the levels of a2M, C3b, and MAC. Co-Immunoprecipitation (Co-IP) was used to pull down CD11b and assess binding to C3b. Confocal microscopy was used to visualize these interactions and light microscopy was used to visualize MAC deposition.

Results RESULTS: MAC was significantly increased on cortical vessels in western analysis. MAC staining of vessels demonstrated a similar distribution to CAA progression. ?2M was significantly decreased in all degrees of CAA compared to AD and controls. C3b was significantly increased in all degrees of CAA compared to controls. Co-IP showed a significantly increased interaction between CD11b and C3b in CAA cases. Western analysis of CD11b IP shows there is an interaction with A?, but only in CAA cases does this occur via C3b. Confocal imaging showed colocalization of CD11b and A? on the plasma membrane of ramified microglia.

Conclusions CONCLUSIONS: This study of human, post-mortem brains with CAA has led to the identification of a novel microglial cell-surface complex that appears to be involved in C3b-mediated A? binding in CAA and may explain the late complement activation on the vessel wall at the site of A? deposition and resulting microbleeds.

Authors/Disclosures
Matthew K. Zabel, PhD (California Northstate University, College of Medicine) PRESENTER	No disclosure on file
Matthew Schrag, MD (Vanderbilt University)	No disclosure on file
Andy Crofton	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Giovanni Coppola, MD (UCLA)	Dr. Coppola has received personal compensation for serving as an employee of Regeneron. Dr. Coppola has received stock or an ownership interest from Regeneron.
Harry Vinters	No disclosure on file
	No disclosure on file
Alastair Compston, PhD, FRCP	No disclosure on file

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