Alpha1-chimaerin, a Rac1 GTPase-activating protein, is expressed at reduced mRNA levels in the brain of Alzheimer's disease patients

Alpha1-chimaerin is a GTPase-activating protein (GAP) for Rac1, a member of the Rho small GTPase family, whose action leads to the inactivation of Rac1. Rac1 activity is upregulated in Alzheimer's disease, but little is known about the role of alpha 1-chimaerin. In this study, we investigated the expression and localization of alpha 1-chimaerin mRNA in postmortem human brains from patients with Alzheimer's disease and control subjects. In situ hybridization studies demonstrated that alpha 1 -chimaerin was expressed by neurons in the neo-cortex of the temporal lobe and the hippocampus of both controls and Alzheimer's disease cases, with the signal intensity dramatically decreased in patients with Alzheimer's disease. Realtime PCR analysis confirmed a significant reduction of alpha 1-chimaerin mRNA expression in the temporal cortex of Alzheimer's disease cases. In contrast, alpha 2-chimaerin mRNA levels showed no significant difference between the groups. The present study showed reduced alpha 1-chimaerin expression in the brain of Alzheimer's disease cases, suggesting a role in the upregulation of Rac1 activity during the disease process. (C) 2015 Elsevier Ireland Ltd. All rights reserved.