A new study links obesity with 21 Alzheimer's disease-related genes.
This may help explain why Alzheimer's is often more frequent among adults who experienced obesity in midlife, according to researchers at the University of Texas Health Science Center at San Antonio.
To study this, the investigators used data from more than 5,600 participants in the long-running Framingham Heart Study to analyze 74 Alzheimer's-related genes.
Of those genes, 21 were either underexpressed or overexpressed in obesity, the research team found. Gene expression refers to the process by which information encoded in a gene is turned into a body function.
The researchers found that 13 Alzheimer's-related genes were associated with body mass index (BMI), an estimate of body fat based on height and weight. Eight genes were associated with waist-to-hip ratio.
“Several of the genes were more strongly related to obesity in midlife versus in late life, and also to obesity in women versus men,” said the study's corresponding author, Claudia Satizabal of the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases at UT Health San Antonio.
These findings are similar to past research that also suggested midlife obesity may be a factor in women's Alzheimer's disease risk, Satizabal said.
People who develop dementia tend to lose weight about five to 10 years before the onset of the disease. It's possible this is an unhealthy weight loss driven by the disease.
“We think it is more important to address obesity and begin healthy weight loss in midlife, in one's 40s and 50s, when obesity may be impacting expression of the genes we studied,” Satizabal said.
While BMI is the classical marker for obesity, some studies suggest that waist-to-hip ratio or belly fat is a more sensitive marker of biochemical abnormalities. Obesity is among the chief risk factors for heart disease and stroke.
The 21 genes that were associated with obesity in this study were implicated in neuro-inflammation, programmed cell death and deposit of amyloid-beta protein in neurons, said study first author Dr. Sokratis Charisis, a resident physician at UT Health's Long School of Medicine.
Eighty-five percent of U.S. adults are projected to be overweight or obese by 2030, the study authors noted in a university news release. Dementia will affect an estimated 131 million people by 2050, so researchers said it's crucial to understand the link between brain health and body weight.
The authors noted that most of the participants in the Framingham Heart Study are white people.
“We think the associations between Alzheimer's-related genes and obesity might be even more relevant in Hispanics, who have a higher prevalence of obesity, but that is yet to be tested,” Satizabal said. “We need to increase the sampling of diverse populations to find more genetic markers related to dementia.”
Researchers plan to expand the biobank at the Biggs Institute.
"We are collecting information and following people over time,” Satizabal said.
Co-author Dr. Sudha Seshadri, a director of the Glenn Biggs Institute and a longtime Framingham researcher, expressed gratitude to participants.
“I am so grateful for the altruism, the time and the trouble taken by our volunteer research participants in Framingham and in San Antonio,” Seshadri said. “They are truly selfless champions helping us uncover the dark secrets of dementia, understand how lifestyle factors change dementia risk, and find new ways to prevent and treat it.”
The study findings were published Feb. 22 in Alzheimer's & Dementia: The Journal of the Alzheimer's Association.
The U.S. Department of Health and Human Services has more about health and being overweight or obese.
SOURCE: University of Texas Health Science Center at San Antonio, news release, Feb. 22, 2023