Dr. Bonnie Lee discusses her research on the primary risk factors for late-onset Alzheimer's disease, including female sex. She explains her current work using mouse models to investigate how menopause models and hormone therapies affect cognitive outcomes based on APOE genotype. Dr. Lee also addresses the historical underrepresentation of women's health in research. Her work aims to inform evidence-based menopausal hormone therapy strategies for females at risk for Alzheimer's.
Full transcript
When we think about risk factors for Alzheimer's disease, we usually start with age and genetics.
Right, like the APOE genotype. But there’s a third factor that affects millions more people, yet it's often overlooked in research.
Simply being female. Women are disproportionately affected by Alzheimer's, but the reasons why have been understudied.
Dr. Bonnie Lee is working to change that. Her research looks at biological events unique to women, like pregnancy and menopause.
These aren't just life stages; they are massive hormonal and immunological shifts. And she's asking how they interact with a person's genetic risk for Alzheimer's.
For example, what if a past pregnancy could change your brain health decades later?
Her research in animal models suggests it does—but not in the way you'd expect. Depending on genetic risk, the effect can be protective, or it can be the opposite.
So what does this mean for the millions of women navigating decisions about things like menopausal hormone therapy? How do you make the right choice when the outcomes are so variable?
That's the core question. To create better prevention strategies, we first have to understand the complexity.
Dr. Bonnie Lee, Sex and Gender-Based Analysis Plus Core at the Centre for Addiction and Mental Health. Tell us about your research. The top non-modifiable risk factors for late-onset sporadic Alzheimer's disease are advanced age, APOE genotype and female sex. Yet, how these factors interact remains poorly understood. My research aims to fill this gap by examining how sex-specific factors influence brain health markers related to Alzheimer's disease. Currently, I'm investigating how different menopause models and hormone therapies alter the progression of cognitive and immune outcomes across APOE genotypes in a mouse model. This research will help inform individualized and evidence-based menopausal hormone therapy strategies to improve prevention approaches for females at risk for Alzheimer's disease. What initially drew me to this field of research was that I've always been fascinated by how sex shapes health outcomes. And I was particularly curious about why females are disproportionately affected by diseases like Alzheimer's disease. I quickly discovered that this question has been vastly understudied and that women's health has historically been underrepresented in research. This really fueled me to contribute to the field and address these knowledge gaps in meaningful ways. Throughout my PhD, I was was driven by the opportunity to study factors unique to females like reproductive history and understand their impact on brain aging and disease risk. I'm excited to continue expanding this work now as a post-doctoral researcher exploring another female specific factor, menopause and the role of menopausal hormone therapy. If there's one key takeaway or message I want people to remember from our research is that influences of sex and health and disease can take many forms and Their effects are not always obvious. It's essential to meaningfully and rigorously investigate both sex and within sex factors to fully understand how diseases develop, progress, and respond to treatment. My research highlights this by showing that a previous pregnancy can have paradoxical effects on key biomarkers of brain health depending on genetic risk for Alzheimer's disease in a rat model. Embracing the heterogeneity within each sex and understanding these complex complex interactions will help transform how we develop diagnostic criteria, preventative strategies, and treatments, moving us closer to truly personalized precision medicine.
So, the takeaway isn't just that sex matters in disease, but that we have to account for the immense heterogeneity within a single sex.
Exactly. Dr. Lee's work shows that a woman’s reproductive history or her menopausal state aren't minor variables. They are distinct biological contexts.
And these contexts interact with genetics, like the APOE genotype, to create very different outcomes for brain health.
The path to precision medicine isn't about one-size-fits-all. It's about building a map that accounts for an individual’s specific biological journey.
Thank you for listening to TRIDENT.
Join us next time.