PROJECT SUMMARY-ANALYTIC CORE C The mission of our Perimenopause in Brain Aging and Alzheimer's Disease Program Project (P3) is to discover biological transformations in brain that occur during the perimenopausal transition that lead to endophenotypes predictive of risk for Alzheimer's disease (AD). Our goals are to identify the mechanisms by which these transformations occur and to translate these discoveries into strategies to prevent conversion to an at-Alzheimer's-risk phenotype. To achieve our Perimenopausal Program Project mission, we have developed a set of integrated program-wide specific aims that span mechanistic discovery to clinical neuroimaging in ApoE genotyped perimenopausal and postmenopausal women to a global population through the ENIGMA network of neuroimages, clinical data and ApoE genetics. The mission of Analytic Core is to provide standardized steroid hormone regimens, sample archiving, processing and distribution, as well as analytic support across the Perimenopausal Program Project. The mission of Analytic Core is to provide standardized steroid hormone regimens, sample archiving, processing and distribution, as well as analytic support across the Program Project. To achieve this mission, the Analytic Core will provide two levels of support. The first level of support entails standardized steroid hormone regimens and sample management. The second level of support entails sample analysis and data interpretation on four major studies: LC-MS/MS steroid analysis, ApoE genotyping, custom array gene expression analysis, and bioinformatic gene functional analysis. Analytic Core was an instrumental and essential resource for the previous Progesterone Program Project and the currently ongoing Perimenopause Program Project. Through the infrastructure and analytic methods it has developed, Analytic Core will continue to play a crucial role in achieving the renewed Perimenopausal Program Project's mission and aims.

PROJECT NARRATIVE – ANALYTIC CORE C ApoE4 is the major generic risk factor for Alzheimer's disease (AD) and women represent ~60% of the AD population. Discovery of at-risk phenotypes and the underlying mechanisms of phenotype development at perimenopausal transition in ApoE4 carriers could potentially lead to the early identification of those at greatest risk of developing AD and interventions to prevent the disease.