Alzheimer’s disease (AD) is strongly influenced by oxidative stress, neuroinflammation, and impaired cellular resilience, all of which are targets of natural antioxidants and nutraceuticals. Yet, individuals show wide variability in their response to such interventions, suggesting a critical role for genetic and epigenetic modifiers. This topic focuses on elucidating the genomic and epigenomic determinants of response to natural antioxidant and nutraceutical therapies in Alzheimer’s disease and related cognitive decline.

Research under this theme will investigate how genetic variation (e.g., SNPs, rare variants, polygenic risk profiles) in genes involved in oxidative stress responses, mitochondrial function, lipid metabolism, and neuroinflammatory pathways modulates the efficacy and safety of nutraceuticals such as polyphenols, carotenoids, omega-3 fatty acids, vitamins, and plant-derived bioactive compounds. Parallel emphasis will be placed on epigenomic mechanisms, including DNA methylation, histone modifications, chromatin accessibility, and non-coding RNAs that are altered in aging and AD, and that may be dynamically reshaped by long-term exposure to these compounds.

The topic encourages studies that:

Integrate multi-omic data (genomics, epigenomics, transcriptomics, metabolomics) to define molecular signatures of responders versus non-responders to specific nutraceutical or antioxidant interventions.

Use patient-derived cells, organoids, animal models, and human cohort data to dissect causal pathways linking nutraceutical exposure to changes in gene regulation, neuronal integrity, and cognitive outcomes.

Explore interactions between age-related epigenetic drift, APOE and other AD risk loci, and diet- or supplement-derived antioxidants in shaping disease trajectory.

Develop biomarkers and predictive models that leverage genomic and epigenomic profiles to stratify patients for personalized nutraceutical strategies in AD prevention and therapy.

By bridging aging biology, nutritional neuroscience, and precision genomics/epigenomics, this topic aims to uncover mechanistic insights into how natural antioxidant and nutraceutical interventions can modify the molecular landscape of aging brains, reduce AD risk, and potentially slow disease progression.

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Genomics and Epigenomics of Natural Antioxidant and Nutraceutical Responses in Alzheimer’s Disease