The mission of our Perimenopause in Brain Aging and Alzheimer's Disease Program Project (P3) is to discover the biological transformations that occur in the brain during the perimenopausal transition which can result in phenotypes predicfive of risk for development of Alzheimer's pathology. We seek to identify the mechanisms by which these changes occur, and translate these discoveries to determine the opfimal timing and strategies for preventing conversion to the perimenopausal at-risk phenotype. To achieve our Perimenopausal Program Project mission, we will determine the perimenopausal phenotypes most at risk for developing biomarkers of Alzheimer's disease;delineate the mechanistic pathways involved in development of these phenotypes;and assess the impact of ovarian hormone and nutritional interventions on expression of Alzheimer's disease biomarkers. 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. To achieve this mission. Analytic Core will provide two levels of support. The first level of support entails Program-wide standardized steroid hormone regimens and sample management, which includes sample procuring, banking, distribufing, sample information recording through the central Integrafive Data Management System, and protein and RNA preparations (Specific Aim 1). The second level of support entails sample analysis and data interpretation on three major studies: (1) LC- MS/MS steroid hormone analysis (Specific Aim 2);(2) custom Taqman low-density array gene expression analysis (Specific Aim 3);and (3) bioinformafic gene funcfional analysis (Specific Aim 4). Analytic Core was an instrumental and essential resource for the currentiy ongoing Progesterone Program Project. Through the infrastructure and analytic methods it has developed. Analytic Core will continue to play a crucial role in achieving the Perimenopausal Program Project's missions and aims.

Public Health Relevance

Women have a higher lifetime risk of developing Alzheimer's disease (AD) and represent -60% of the AD population. Discovery of at-risk phenotypes and the underiying mechanisms of phenotype development at perimenopausal transition could potentially lead to the eariy identification of those at greatest risk of developing AD and intervenfions to prevent the disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG026572-08
Application #
8532784
Study Section
Special Emphasis Panel (ZAG1-ZIJ-8)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
8
Fiscal Year
2013
Total Cost
$304,779
Indirect Cost
$119,033
Name
University of Southern California
Department
Type
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Uchoa, Mariana F; Moser, V Alexandra; Pike, Christian J (2016) Interactions between inflammation, sex steroids, and Alzheimer's disease risk factors. Front Neuroendocrinol 43:60-82
Yin, Fei; Sancheti, Harsh; Patil, Ishan et al. (2016) Energy metabolism and inflammation in brain aging and Alzheimer's disease. Free Radic Biol Med 100:108-122
Finch, Caleb E; Shams, Sara (2016) Apolipoprotein E and Sex Bias in Cerebrovascular Aging of Men and Mice. Trends Neurosci 39:625-37
Cacciottolo, Mafalda; Christensen, Amy; Moser, Alexandra et al. (2016) The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice. Neurobiol Aging 37:47-57
Rettberg, Jamaica R; Dang, Ha; Hodis, Howard N et al. (2016) Identifying postmenopausal women at risk for cognitive decline within a healthy cohort using a panel of clinical metabolic indicators: potential for detecting an at-Alzheimer's risk metabolic phenotype. Neurobiol Aging 40:155-63
Finch, Caleb E; Crimmins, Eileen M (2016) Constant molecular aging rates vs. the exponential acceleration of mortality. Proc Natl Acad Sci U S A 113:1121-3
Finch, Caleb E; McMahon, Andrew P (2016) Stem cells for all ages, yet hostage to aging. Stem Cell Investig 3:11
Karim, Roksana; Dang, Ha; Henderson, Victor W et al. (2016) Effect of Reproductive History and Exogenous Hormone Use on Cognitive Function in Mid- and Late Life. J Am Geriatr Soc 64:2448-2456
Wang, Yiwei; Brinton, Roberta D (2016) Triad of Risk for Late Onset Alzheimer's: Mitochondrial Haplotype, APOE Genotype and Chromosomal Sex. Front Aging Neurosci 8:232
Moser, V Alexandra; Pike, Christian J (2016) Obesity and sex interact in the regulation of Alzheimer's disease. Neurosci Biobehav Rev 67:102-18

Showing the most recent 10 out of 87 publications