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Alzheimer’s Disease: a case of evolutionary mismatch?

This conversation was led by Molly Fox, Assistant Professor of Anthropology and Psychiatry & Biobehavioral Sciences at UCLA. Alzheimer’s Disease (AD) is a devastating, neurodegenerative disorder that emerges after age 65, afflicting ~20% of women and ~10% of men. A clear, singular cause of AD remains elusive; rather, it is thought to be the result of a complex interplay between physiological, genetic, and environmental risk factors and vulnerabilities. Several risk factors and prodromal phenotypes associated with AD were likely absent or at far lower frequency for the vast majority of human evolutionary history, suggesting the possibility that AD may be a case of “evolutionary mismatch.” My research in this area focuses on two domains of human life that have changed profoundly in recent history: female reproductive life-history patterns and microbial exposures. In this context, I explore how immune function and endocrinology act as key mediators of the journey from risk factors to pathogenesis. I argue that it is particularly important to examine AD risk and etiology in women, because post-menopausal women have opportunity to engage in activities that promote inclusive fitness, and those suffering from AD would not only miss out on these opportunities, but may even be burdensome to younger kin in ways that undermine inclusive fitness. Women are more likely to develop AD than age-matched men, and AD is associated with distinct biomarkers among women and men, justifying the need to investigate female-specific etiologies.

Molly Fox in a Zoom meeting

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