Obesity linked to 21 genes related to Alzheimer’s disease, study finds

Obesity is a disease affecting the entire body and its health. A person is obese if their weight is higher than what is normally considered healthy for their height, also known as their body mass index (BMI).

Previous research suggests that maintaining an appropriate BMI for height may help decrease the risk for Alzheimer’s disease. Additionally, a recent study found the type of neurodegeneration caused by obesity is similar to the type causing Alzheimer’s disease, suggesting that controlling weight could help slow cognitive decline and lower a person’s risk for Alzheimer’s.

Past research shows obesity causes inflammation in the body, which can lead to not only an increased risk for Alzheimer’s but other diseases including cardiovascular disease, diabetes, and stroke.

According to Dr. Claudia Satizabal, assistant professor at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases and The University of Texas Health Science Center at San Antonio and the study’s corresponding author, the team decided to look for a genetic link between obesity and Alzheimer’s disease because, from previous studies, we know that obesity — particularly in midlife — is a risk factor for Alzheimer’s disease dementia, but we don’t completely understand why.

“Thus, we asked the question, what if obesity changes the expression of key genes implicated in Alzheimer’s that could help explain some of the mechanisms linking these two conditions?” she told Medical News Today.

For this study, Dr. Satizabal and her team analyzed 74 Alzheimer’s-related genes from over 5,600 participants of the Framingham Heart Study.

Upon analysis, researchers discovered of those 74 genes, 21 were either under-expressed or over-expressed in obesity. Additionally, scientists found 13 Alzheimer’s-related genes were associated with BMI, and eight were linked to waist-to-hip ratio.

“We were expecting some associations because recent genetic studies of Alzheimer’s dementia have pointed to genes involved in the metabolism of lipids and the immune system, both of which can be dysregulated in obesity,” Dr. Satizabal explained. “However, we were a little surprised to see as many — the expression of almost 30% of the Alzheimer’s disease genes showed links with obesity traits.”

Dr. Satizabal said although they cannot derive immediate recommendations for patients from this study, these results add to the growing literature linking obesity and Alzheimer’s dementia.

“It is important to discuss with patients the implications of excess weight, especially abdominal obesity, to preserve cardiovascular and brain health as we age,” she added.

Researchers mentioned this study’s limitation as most data from the Framingham Heart Study was from a mostly white population.

“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 says. “We need to increase the sampling of diverse populations to find more genetic markers related to dementia.”

As for the next steps in this research, Dr. Satizabal said, “We are planning to replicate these findings in additional, more diverse samples, and follow up on key cellular and molecular mechanisms.”

Medical News Today also spoke about this study with Dr. Santosh Kesari, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA and regional medical director for the Research Clinical Institute of Providence Southern California.

He said he was not surprised by the study’s findings because we know chronic diseases such as obesity cause all kinds of problems, including dementia.

“It was interesting to find which genes, but at the same time it wasn’t completely surprising that there would be a set of genes that could explain the risk of neurodegenerative diseases in patients with obesity,” he added.

When asked what the correlation between obesity and Alzheimer’s disease might be, Dr. Kesari said we do not yet know the full story.

“It seems some of the story is in this new publication because some of the genes involved that are related to obesity and increased risk of Alzheimer’s in this dataset highlight the role of neuroinflammation,” he continued. “At least a few of the genes are linked. We know obesity causes inflammation and some of those same genes seem to be implicated in neuroinflammation, which we think is one of the underlying mechanisms of dementia, including Alzheimer’s dementia.”

For people at high risk for Alzheimer’s disease, Dr. Kesari said the earlier they can start preventive measures, the better.

“If you have the genetic risk for Alzheimer’s, you know that in your 40s or 30s, you start to change your lifestyle and habits to prevent problems occurring decades down the line,” he explained. “And if obesity is one problem that also is related to Alzheimer’s, certainly reducing weight in your 30s and 40s will reduce the risk of dementia decades later.”

“For diseases such as Alzheimer’s, knowing your risk and what you can do decades before is going to be the biggest step to preventing it,” Dr. Kesari added. “Once you have dementia when you’re overweight, obviously [weight] reduction is still important for your general health, but it may not make much difference in terms of dementia that’s already set in. Those studies need to be done as well.”