How Ovarian Immune Cells May Shape Alzheimer’s Risk

The goal of this project is to determine whether inflammatory macrophages in the aging ovary drive brain inflammation, Alzheimer’s disease pathology, and cognitive decline, and to identify ovarian-derived signals that could serve as new biomarkers or therapeutic targets for women’s brain health.

Women are more likely to develop Alzheimer’s disease, but the reasons why are not fully understood. This project explores how immune cells in the aging ovary may send signals to the brain that worsen memory problems and drive disease. By studying ovarian immune aging in Alzheimer’s mouse models, we aim to discover new ways the body’s own immune system may influence brain health and reveal novel targets for protecting women’s memory as they age.

This proposal is innovative because it reframes the aging ovary as a peripheral immune organ that may actively drive female-biased Alzheimer’s disease risk, rather than focusing only on estrogen loss or brain-intrinsic mechanisms. By combining ovarian transplantation with macrophage depletion in amyloid and tau models, we will directly test whether ovarian macrophages causally promote neuroinflammation, pathology, and cognitive decline. We will also identify conserved ovary-to-brain inflammatory signals as potential biomarkers or therapeutic targets.

Once complete, this study could identify a new biological pathway linking ovarian aging to brain inflammation, Alzheimer’s disease progression, and cognitive decline, helping explain why women are disproportionately affected by AD. For the research field, the project will provide causal evidence, molecular datasets, and candidate circulating factors that may shift how investigators study menopause, systemic inflammation, and brain aging. For the general public, these findings could support future development of non-hormonal biomarkers or interventions aimed at preserving women’s brain health during aging.