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 #
5P01AG026572-09
Application #
8721280
Study Section
Special Emphasis Panel (ZAG1-ZIJ-8)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
9
Fiscal Year
2014
Total Cost
$323,499
Indirect Cost
$126,943
Name
University of Southern California
Department
Type
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Riedel, Brandalyn C; Daianu, Madelaine; Ver Steeg, Greg et al. (2018) Uncovering Biologically Coherent Peripheral Signatures of Health and Risk for Alzheimer's Disease in the Aging Brain. Front Aging Neurosci 10:390
Scheyer, O; Rahman, A; Hristov, H et al. (2018) Female Sex and Alzheimer's Risk: The Menopause Connection. J Prev Alzheimers Dis 5:225-230
Geifman, Nophar; Kennedy, Richard E; Schneider, Lon S et al. (2018) Data-driven identification of endophenotypes of Alzheimer's disease progression: implications for clinical trials and therapeutic interventions. Alzheimers Res Ther 10:4
Walters, Michelle J; Sterling, Joanna; Quinn, Crystal et al. (2018) Associations of lifestyle and vascular risk factors with Alzheimer's brain biomarker changes during middle age: a 3-year longitudinal study in the broader New York City area. BMJ Open 8:e023664
Mosconi, Lisa; Brinton, Roberta Diaz (2018) How would we combat menopause as an Alzheimer's risk factor? Expert Rev Neurother 18:689-691
Mosconi, Lisa; Walters, Michelle; Sterling, Joanna et al. (2018) Lifestyle and vascular risk effects on MRI-based biomarkers of Alzheimer's disease: a cross-sectional study of middle-aged adults from the broader New York City area. BMJ Open 8:e019362
Moser, V Alexandra; Uchoa, Mariana F; Pike, Christian J (2018) TLR4 inhibitor TAK-242 attenuates the adverse neural effects of diet-induced obesity. J Neuroinflammation 15:306
Berkowitz, C L; Mosconi, L; Rahman, A et al. (2018) Clinical Application of APOE in Alzheimer's Prevention: A Precision Medicine Approach. J Prev Alzheimers Dis 5:245-252
Gahm, Jin Kyu; Shi, Yonggang; Alzheimer’s Disease Neuroimaging Initiative (2018) Riemannian metric optimization on surfaces (RMOS) for intrinsic brain mapping in the Laplace-Beltrami embedding space. Med Image Anal 46:189-201
Mosconi, Lisa; Berti, Valentina; Quinn, Crystal et al. (2017) Sex differences in Alzheimer risk: Brain imaging of endocrine vs chronologic aging. Neurology 89:1382-1390

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