Grant: Project Grant

Alzheimer's disease (AD) is an irreversible, progressive brain condition that affects memory and intellectual skills. People suffering from dementia due to AD lose their autonomy and cannot carry out the simplest tasks. Although dementia symptoms typically emerge after 65 years, the progressive accumulation of toxic proteins (amyloid and tau proteins) starts 20 years before. For unknown reasons, 2/3 of dementia patients are females. Women have more toxic tau in the brain as compared to men. There is mounting evidence that menopause can enhance amyloid and tau aggregation in the brain, and hormone replacement therapy might be beneficial; however, these effects, if existent, have never been demonstrated in living post-menopausal women. Recent advances in scan technology now allow us to study the progression of brain amyloid and tau at its earliest stages. One can measure the earliest alterations associated with amyloid and tau in the brain with blood or spinal tap measures. In this proposal, we will use brain scans to understand whether menopause triggers the silent phases of AD (presence of brain amyloid and tau without cognitive changes). We also want to know whether hormone replacement therapy for menopause might be beneficial to mitigate the accumulation of amyloid and tau in the silent phase of AD. To this end, we will compare the rate of tau accumulation between males and females exposed and not exposed to hormone replacement therapy for menopause. We will conduct PET scans on participants in their early 50-60 to assess the earliest amyloid and tau accumulation stage. We plan to repeat these scans 18 months later to assess the tau accumulation rate. These results will help researchers to better understand the role of sex as a risk factor for developing brain protein aggregation and dementia. Importantly, it will allow personalized dementia prevention for females as early as late middle age.