Alzheimer’s: Genetic Variants Mediate Effects of Poor Diet in Cognitive Decline Interview with:

Dr. Dunn

Dr. Amy Dunn, PhD
Kaczorowski lab
The Jackson Laboratory What is the background for this study? What are the main findings?

Response: Environmental factors, such as a poor diet, are known risk factors for Alzheimer’s disease. But the mechanisms are complex, and it is not known how such environmental perturbations interact with individual genetic variation to confer disease risk. Previous studies have not adequately addressed how the combination of genetic variant and environmental factors combine to alter cognitive response to a poor diet.

To investigate gene-by-environment interactions, we fed either a normal diet or a high-fat diet to a genetically diverse Alzheimer’s disease mouse model population starting at six months of age and monitored metabolic and cognitive function.

We observed accelerated working memory decline in the mice on the high-fat diet after eight weeks, with substantial gene-by diet effects on both cognitive and metabolic traits.

Metabolic dysfunction was more closely related to cognitive function in mice carrying Alzheimer’s mutations than in those without. Interestingly, the high-fat diet affected metabolic function differently in female versus male mice. What should readers take away from your report? 

Response: The study demonstrated gene-by-diet interactions in Alzheimer’s disease symptoms, meaning that there are genetic variants that mediate the effect of a poor diet on cognitive decline. Identifying these variants and the roles they play in disease risk and onset may provide an opportunity to apply them to humans and develop personalized strategies to prevent Alzheimer’s disease or effectively intervene in its early stages. Lifestyle intervention strategies, such as improving diet, are becoming more popular; while eating a healthier diet is likely beneficial overall, there may be people who will particularly benefit from avoiding high-fat, high-sugar diets, and other people may experience less of a benefit. Results from our study will help to identify such individuals. What recommendations do you have for future research as a result of this work?

Response: Future research is needed to identify the gene variants that contribute to cognitive decline or resilience in response to a poor diet. What are their functions? What are other genetic factors that modulate the effects of other environmental factors (e.g., exercise), and how can we leverage these to improve personalized treatments for Alzheimer’s? Effective treatments for Alzheimer’s will likely not be a one-size-fits-all solution given how heterogenous the disease and its etiology are. Understanding how genetic and environmental factors interact in disease pathogenesis will help us to identify the best treatments and preventative measures for patients given their individual genetic and environmental risk “profile.” 

Citation: Alzheimer’s Association International Conference (AAIC) in Los Angeles this month (July 14-18, 2019).

P4-088 Gene-By-Environment Regulation of Alzheimer’s Disease Pathogenesis
Poster, Wednesday, July 17, 9:30-4:15, Catherine Kaczorowski
Poster #32423

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Jul 31, 2019 @ 2:20 am

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