Alpha Omega Alpha Honor Medical Society

2012 Research Abstract

The role for microglial Fractalkine signaling in complement-mediated vascular fragility of cerebral amyloid angiopathy

Investigator: Nicholas Will, Loma Linda University School of Medicine

Mentor: Wolf M. Kirsch, MD, Neurosurgery Center for Research, Training, and Education, Loma Linda, California

Alzheimer’s disease (AD) is the most common neurodegenerative disease and often co-manifests with cerebral amyloid angiopathy (CAA) resulting in significant cognitive impairment. Both of these diseases are poorly understood and therefore lack effective treatments. The objective of this study was to investigate a possible role for Fractalkine (CX3CL1), an important regulator of microglia in the brain, in the pathogenesis of the microbleeds observed in CAA. More specifically this study examined if a decrease in Fractalkine signaling leads to an increase in microglial CD11b expression and C3b-mediated amyloid-beta (Aβ) uptake, resulting in complement activation and blood vessel damage. To test this hypothesis, BV-2 mouse microglia were incubated with Aβ, Fractalkine, or a Fractalkine inhibitory antibody. Relative levels of the Fractalkine receptor (CX3CR1) and C3b proteins were determined using western blots. There was no significant difference between the groups indicating that Fractalkine may not affect CX3CR1 or C3b levels and that Fractalkine signaling is less likely involved in the pathogenesis of CAA via this mechanism. Further research with refined techniques and a larger sample size are necessary to either support or refute this conclusion.

Updated on August 5, 2013.


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