Dietary responses of dementia-related genes encoding metabolic enzymes

Authors: Parnell, Laurence; MAGADMI, ROZANA - Tufts University; ZWANGER, SLOANE - Skidmore College; Shukitt-Hale, Barbara; Lai, Chao Qiang; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/24/2023
Publication Date: 1/27/2023
Citation: Parnell, L.D., Magadmi, R., Zwanger, S., Shukitt Hale, B., Lai, C., Ordovas, J.M. 2023. Dietary responses of dementia-related genes encoding metabolic enzymes. Nutrients. 15(3):644. https://doi.org/10.3390/nu15030644.
DOI: https://doi.org/10.3390/nu15030644

Interpretive Summary: As the population ages, dementia is becoming an affliction of increasing concern. This project assessed the activity of a set of dementia-related genes in 12 different non-brain tissues, including whole blood, finding that two-thirds of the dementia genes are more active in non-brain tissues than in brain. The research also determined how the activity of these genes responds to the intake of various foods, minerals and vitamins present in the regular diet. The analyses identified several genes relevant to dementia and active in basic metabolic processes outside the brain. Furthermore, it was determined that several of these genes are responsive to the intake of specific foods. These findings reveal that tissues external to the brain respond to dietary components and can support brain health and diminish neurodegeneration. Further experiments are needed to extend these preliminary findings.

Technical Abstract: The age-related loss of cognitive function is a growing concern for global populations. Many factors that determine cognitive resilience or dementia also have metabolic functions. However, this duality is not universally appreciated when the action of that factor occurs in tissues external to the brain. We examined a set of genes involved in dementia, i.e., those related to vascular dementia, Alzheimer disease, Parkinson disease, and human metabolism for activity in 12 metabolically active tissues. Mining the Genotype-Tissue-Expression (GTEx) data showed that most of these metabolism-dementia (MD) genes (62 of 93, 67%) exhibit higher median expression in any of the metabolically active tissues than in the brain. After identifying that several MD genes served as blood-based biomarkers of longevity in other studies, we examined the impact of intake of food, nutrients and other dietary factors on expression of MD genes in whole blood in the Framingham Offspring Study (n = 2134). We observed positive correlations between flavonoids and HMOX1, taurine and UQCRC1, broccoli and SLC10A2, and myricetin and SLC9A8. In contrast, dairy protein and palmitic acid were negatively correlated, respectively, with the expression of IGF1R and CSF1R (P < 2.92E-04). The results of this investigation underscore the potential contributions of metabolic enzyme activity in non-brain tissues to dementia risk. Specific epidemiological or intervention studies could be designed using specific foods and nutrients that influence the expression of some MD genes to verify the findings presented here.