ISOA funding has enabled us to discover and characterize the neurogenic and behavioral efficacy of allopregnanolone (AP) as a therapeutic agent in the triple transgenic mouse model of Alzheimer's disease and human neural progenitor cells (see accompanying Brinton ISOA 2 year Progress Report). Results of these analyses were the foundation upon which we constructed a successful NIA UO1 proposal to conduct preclinical IND enabling research. Peer review of the proposal resulted in a high priority score (129) and percentile rank (4.7%) predictive of funding. NIA Council is scheduled to meet in October 2007 and funding is projected to begin in December although delay until January is anticipated.This proposal requests bridge funds to sustain our therapeutic development momentum until our NIA UO1 begins which we project will be in January 2008. Bridge support is requested to achieve the following objectives: 1) to sustain our triple transgenic Alzheimer's (3xTgAD) and background non-transgenic mouse colonies; 2) to continue ongoing neurogenic and behavioral analyses of APalpha efficacy in 3xTgAD mice with mild to moderate AD pathology burden and 3) to begin preliminary analyses to determine the optimal route of APalpha administration.