Studying Biological Sex-Based Differences in Alzheimer’s Disease

This initiative investigates the biological and environmental mechanisms that drive sex-based differences in Alzheimer’s Disease. By analyzing why disease prevalence, risk factors, and progression trajectories differ between men and women, the focus aims to shift toward precision diagnostics and personalized therapies. The study specifically accounts for unique female risk factors, such as reproductive history and perimenopausal changes, alongside shared factors like vascular health and neuroinflammation.

 

1.     Biological Mechanisms: Examining sex-specific immune responses ("inflammaging") and neurodegenerative markers (Tau PET, Nf-L levels, and skin-based Lewy pathology) to identify distinct clinical targets.

2.     Vascular & Social Determinants: Assessing how differences in Social Determinants of Health  and Vascular Risk Factors contribute to cognitive reserve and neurodegeneration in each sex.

3.     Longitudinal Progression: Utilizing Latent Class Analysis (LCA) and mixed-effects models to track how sex interacts with age and genetics (APOE) to influence the transition from Mild Cognitive Impairment (MCI) to dementia.

4.     Biomarker Sensitivity: Evaluating blood, skin, and imaging biomarkers to ensure diagnostic reliability across both sexes, particularly in cases of co-pathologies.

 

By identifying the divergent "tipping points" for cognitive decline in men versus women, this research will lead to more accurate risk-prediction models. The findings will ensure that future clinical trials and treatments are tailored to the specific biological profiles of each sex, ultimately reducing the disproportionate burden of Alzheimer’s disease on women and improving diagnostic accuracy for all patients.