The mission of our Perimenopause in Brain Aging and Alzheimer's Disease Program Project (P3) is to discover the biological changes that occur in the brain during the perimenopausal transition which can result in phenotypes predictive 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 optimal timing and strategies for preventing conversion to the perimenopausal at-risk phenotype. To achieve our mission, we will determine the perimenopausal phenotypes associated with different cycle transition states;delineate the mechanistic pathways involved in cJevelopment of these phenotypes;and assess the impact of ovarian hormone and high-fat diet induced obesity (DIO) on expression of Alzheimer's disease biomarkers. The mission of Animal Core (Core B) is to ensure the success ofthe Perimenopause Program Project through provision of animals as neecled to Projects 1-3. To achieve its mission. Animal Core will develop rodent models of perimenopause and menopause;maintain and track animals from acquisition or birth, though determination of cycling status, study enrollment, experimental manipulation, to fissue collection across the entire Perimenopause Program Project;and obtain tissue samples for storage and genetic analyses by Analytic Core.

Public Health Relevance

(See Instructions): The complexity of the perimenopausal process has been a major barrier to both basic and clinical research of this aging transition in women. Development of rodent models ofthe human perimenopause is critical to advancing knowledge ofthe effects ofthe perimenopause on the brain, identifying phenotypes at risk for age-associated neurological diseases, and developing strategies that promote healthy neurological aging in women to prevent age-associated diseases such as Alzheimer's.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAG1-ZIJ-8)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Southern California
Los Angeles
United States
Zip Code
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