ADAP1/Centaurin-α1-Bid Signaling in Alzheimer’s Disease

Abstract

Previous studies from our lab found that the brain-specific Ras-anchoring protein, ADAP-1/Centaurinα1 (CentA1) is required for Aβ42-induced neuronal dysfunction (Szatmari et al., 2013). Transcriptome profiling of the forebrain of wild type, CentA1, hAPP-J20, and hAPP-J20 x CentA1 KO mice was performed and found Bid was a differential expressed gene between genotypes. Plotting the pathway scores produced by comparing the expression of 880 genes using NanoString’s mouse Neuropathology and Neuroinflammation gene expression panels found differences in multiple pathways related to apoptosis and gliosis. At the individual gene level, CentA1 KO reduced the level of the pro-apoptotic protein Bid. Purpose: The goal of my research is to determine the role of the pro-apoptotic protein Bid, in the rescue of AD-like phenotypes in AD model mice lacking Centaurinα1 (hAPP-J20 x CentA1 KO mice).