Abstract
Alzheimer's disease (AD) is characterized by amyloid β (Aβ) deposition, tau pathology, cerebrovascular damage, and microglia‐mediated neuroinflammation. Cerebrovascular damage includes breakdown of the blood‐brain barrier leading to fibrinogen deposition in the AD brain. Fibrinogen is a blood coagulation factor that upon conversion to fibrin binds to the CD11b/CD18 receptor and induces microglial activation. Here, we show that genetic disruption of fibrinogen interaction with the CD11b/CD18 receptor in 10‐month‐old 5XFAD mice crossed with Fggγ390–396A knock‐in mice, which lack the CD11b binding site, have less neuropathology and microglial activation than 5XFAD littermates. Comparative histological analyses revealed reductions in neuronal and presynaptic terminal loss, Iba‐1+ microglia, immunostaining for the lysosomal marker LAMP‐1, and Aβ plaque burden in the hippocampus of 5XFAD:Fggγ390–396A mice. Thus, genetic inhibition of fibrinogen interaction with CD11b/CD18 receptor reduces multiple AD‐relevant neuropathological alterations in 5XFAD mice.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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