ABI3 deletion in TgCRND8 mice is associated with reduced amyloid plaque pathology and altered glial response.

Abstract

Recent genome-wide association studies (GWAS) have identified several rare coding variants in a cluster of immune-related genes that are significantly associated with Alzheimers disease. This includes the risk variant (S209F) in ABI3, a gene encoding the Abl Interactor family member 3 protein that is highly expressed in microglia, but little is known about its function in these cells and its association with AD. We have investigated the effects of ABI3 deletion on AD pathological features in the transgenic (Tg) CRND8 APP mouse model by immunofluorescence (IF) staining and confocal microscopy. We have observed that ABI3 expression is localized to microglia in the mouse brain and that the ABI3 immunoreactivity levels are increased in the TgCRND8 mice. The loss of ABI3 leads to a significant reduction of amyloid plaque numbers and size in the 9-month-old TgCRND8 mice. This is also accompanied by a reduced number of microglia clustering around the plaques. On the basis of these observations, we hypothesize that the loss of ABI3 may lead to changes in microglial behavior which directly or indirectly leads to reduced AD pathology in mice.