The Jackson Laboratory

Alzheimer’s Disease: Genes Modify Effect of High Fat Diet Interview with:
The Jackson LaboratoryCatherine Kaczorowski, Ph.D.

Associate Professor and Evnin Family Chair in Alzheimer’s Research
Kristen O’Connell, Ph.D., Assistant Professor
Amy Dunn, Ph.D., Postdoctoral Associate
The Jackson Laboratory What is the background for this study? What are the main findings?

Dr. Amy Dunn: “Alzheimer’s disease is complex, with both genetic and environmental factors determining symptom onset and disease progression, though our current understanding of how genetic and environmental factors interact to influence disease risk is incomplete. We recently developed a panel of genetically diverse mice carrying human familial AD mutations (AD-BXDs) that better model human AD in order to determine how genetics and diet interact to modify disease onset and severity.

We fed a high fat diet to AD-BXDs and monitored metabolic and cognitive function over the duration of the HFD feeding.  We observed accelerated working memory decline in most of the AD-BXD mouse strains, however, the impact of high fat diet on memory was dependent on individual genetic differences across the panel, with some AD-BXD strains maintaining cognitive function on high fat diet (resilient strains).

Our data suggest that diet and genetic background interact to mediate vulnerability to AD pathogenesis, and that metabolic factors (e.g. obesity, body composition) that may contribute to cognitive decline differentially in normal aging versus AD. “

Dr. Kristen O’Connell: “We also found that sex plays a critical role in determining the impact of high fat diet and body weight on the onset and severity of memory deficits, with females exhibiting more rapid decline, paralleling what has been reported in humans. These data suggest that incorporation of genetic diversity into existing models of AD dramatically enhances their translational relevance and emphasizes the need to include both males and females in preclinical studies.

Our panel can now be used to identify the mechanisms underlying how and why certain individuals are more susceptible (or resilient) to developing Alzheimer’s disease based on their genetics and environment.  “ What should readers take away from your report?

Dr. Catherine Kaczorowski: There are individual differences in how vulnerable people are to environmental risk factors for Alzheimer’s disease. Identifying the genetic bases for these differences is difficult to do in humans, so my lab developed the first mouse model of Alzheimer’s disease that will allow us to tease apart these gene-by-environment interactions. Future analyses will identify the genetic and molecular targets contributing to Alzheimer’s disease pathogenesis that may be exploited to delay, prevent or even cure the disease.” What recommendations do you have for future research as a result of this work? 

Dr. Amy Dunn: “Alzheimer’s disease is a highly complex disease with many contributing genetic and environmental factors. Understanding how these factors interact to determine disease risk and progression will be important in understanding how to best treat the disease in a patient-by-patient manner. By focusing on these individual variations in disease vulnerability in the future, we will improve our ability for individualized therapeutic strategies and multi-scale interventions to better combat Alzheimer’s disease. “  


Gene x Diet Interactions Modify Symptoms of Alzheimer’s Disease

(Poster AAIC 2018, Sunday July 22) 

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Last Updated on July 31, 2018 by Marie Benz MD FAAD