PI: Roberta Diaz-Brinton
Institution: University of Arizona


Alzheimer’s disease (AD) has a protracted preclinical phase that suggests that events early in the aging process can initiate vulnerability to late onset AD. The greatest risk factors for AD are age, the APOE4 genotype and female sex. Each year ~1.5 million American women enter into the perimenopause, a neuroendocrine transition state unique to the female. The mission of this Perimenopause in Brain Aging and Alzheimer’s Disease Program Project (PBA-AD) is to discover biological transformations in brain that occur during the perimenopausal transition that lead to endophenotypes predictive of risk of 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. In the PBA-AD project, we will acquire multimodal imaging data from ApoE genotyped perimenopausal and postmenopausal women to test the hypothesis that ApoE4 positive females experience a triple hit: 1) ApoE4 genotype; 2) Aging and 3) Perimenopause. With this collaborative project between LONIR P41 project and PBA-AD project, we will leverage and drive the development of novel computational techniques that will advance the scientific studies for gaining insights into the mechanisms underlying the heightened risk of AD in APOE4 positive females and identifying potential therapeutic targets and opportunities.