Alzheimer’s Disease Risk Factors & Sex-Specific Mechanisms – Silvia Maioli's research group

🧬 Cholesterol, Brain Health & Alzheimer’s
Alterations in brain cholesterol metabolism are central to neurodegenerative processes. We explore how the APOE4 genotype, brain cholesterol turnover, and cholesterol-derived metabolites (such as oxysterols) influence cognitive function and AD progression.

🧠 Sex Differences in Alzheimer’s Risk
Women are at a higher risk for Alzheimer's disease (AD), partially due to hormonal changes, among other factors, that affect brain metabolism. Our research investigates how sex hormones, cholesterol metabolism, and genetic factors contribute to sex-specific disease pathways and influence treatment responses.

🔬 CYP46A1 as a Therapeutic Target for women at risk 
Our research has shown that overexpressing CYP46A1 improves memory in aging and estrogen deprived female mice. We explore pharmacological and genetic strategies to increase CYP46A1 activity as a potential neuroprotective therapy for women at higher risk of AD.

🔍 Early Biomarkers for Women at Risk
We analyze biomarkers in blood and cerebrospinal fluid, such as cholesterol metabolites, to identify high-risk women and improve early detection strategies for AD.

💊 Multi-Drug Therapies & Sex-Specific Effects
Many older adults, including AD patients, take multiple medications (polypharmacy), but their effects differ by sex. We investigate how commonly prescribed drug combinations impact cognition, metabolism, and AD progression using preclinical models and human cohort data to guide personalized treatment strategies .

Julen Goicolea, 2021: Translational studies on Alzheimer’s disease : a focus on cholesterol metabolism, thioredoxin-80 and microglia function

María Latorre Leal, 2024: The role of oxysterols in neurodegeneration : implications for cognitive function, maternal effects, and sex-specific differences