Mouse study shows how a high-fat diet may heighten risk

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Animal research sheds light on the mechanisms through which a high-fat diet may increase Alzheimer’s risk. Image credit: FG Trade/Getty Images.
  • Dementia is a growing concern, with worldwide numbers predicted to rise to more than 150 million by 2050.
  • Research has linked diets high in fat, particularly saturated fat, with Alzheimer’s disease and other forms of dementia.
  • However, the mechanisms by which a high-fat diet increases the risk are unclear.
  • Now, research has found changes in molecular markers related to Alzheimer’s development in mice fed a high-fat diet.
  • More research is needed to determine whether similar effects are seen in people and whether limiting fat intake might reduce Alzheimer’s risk.

According to the World Health Organization (WHO), of the approximately 55 million people worldwide who live with dementia, up to 70% have Alzheimer’s disease. The number of people with dementia is increasing rapidly, with that number projected to rise to more than 150 million people by 2050.

Lifestyle factors, such as lack of exercise, an unhealthy diet, smoking and alcohol consumption increase the risk of cognitive decline and Alzheimer’s disease. Several studies have shown that a high intake of saturated fat is a major risk factor for Alzheimer’s.

Stefania Forner, PhD, Alzheimer’s Association director of Medical and Scientific Relations told Medical News Today why these lifestyle factors might increase the risk.

“Obesity is associated with an increased risk of type 2 diabetes, high blood pressure, and blood vessel disorders that impact multiple systems in the body, including the brain,“ she explained. “These conditions may increase the risk of developing Alzheimer’s disease in older adults.”

“Nutrition also may play an important role in brain health and the risk for developing Alzheimer’s later in life,” she added.

A new study, in mice, has now uncovered a molecular mechanism that could explain why a high-fat diet increases the risk of Alzheimer’s.

The research is published in the journal Nutrients.

The researchers used transgenic APP/PS1 mice that develop characteristics of Alzheimer’s disease, such as elevated beta-amyloid and cognitive impairment, with wild-type mice as controls.

At 21 days of age, the researchers randomly allocated the mice to normal feed or a 60% fat diet (high-fat diet), which they then fed them for 6 months. During this time, the researchers monitored the rodents’ food consumption and weighed them regularly. They also tested their glucose and insulin tolerance.

The mice on the high-fat diet, as expected, gained more weight than the mice on the normal diet. They also had worse glucose (blood sugar) and insulin metabolism than the mice on the normal diet.

After 6 months, the researchers killed the mice humanely, and extracted ribonucleic acid (RNA) from their serum, cortex and hippocampus for testing.

In earlier studies, the researchers found that “feeding APP/PS1 mice with [a high-fat diet] aggravated the animals’ learning and memory abilities together with increasing neuroinflammation, brain [beta-amyloid] production and plaque burden”.

When they looked at the RNA for both types of mice, they found that as well as metabolic changes, the mice on the high-fat diet showed several differences in miRNA from those on the regular diet.

In the study paper, the researchers state that “[t]hese findings support an active role of these miRNAs in the progression of neurodegeneration aggravated by the metabolic misbalance produced by consuming a high-fat diet.”

The changes they found in miRNA are linked to processes that can cause brain damage, such as the accumulation of beta-amyloid plaques, excessive production of tau protein — both of which are markers of Alzheimer’s — and inflammation in the brain.

Forner, who was not involved in the study, explained what these findings might mean:

“Using a mouse model of Alzheimer’s, this study sheds some light on how a high-fat diet may affect insulin-resistant microRNAs, which help determine what genes are turned ‘off’ or ‘on,’ including in areas of the brain related to memory and cognition.“

“However,” she told MNT, “this study has limitations, including: (a) they only investigated male mice, and (b) they did not look at the role of fat cells, other organs, and other brain areas.”

Lead researcher Mònica Bulló, professor at the Department of Biochemistry and Biotechnology and member of the Metabolic Health and Nutrition unit and the Environmental, Food and Toxicological Technology Centre (TecnATox) of the URV, said in a news release that “[t]he results of this study are a step forward in our understanding of this disease and may explain the relationship between obesity, type 2 diabetes and the onset of Alzheimer’s.“

“The findings also offer new targets for the possible prevention and treatment of the disease,” she added.

However, it must be noted that results in mice do not always translate to people. Forner emphasized:

“This study is based on research in a mouse model of Alzheimer’s. While animal models of the disease are somewhat similar to how Alzheimer’s progresses in humans, they do not replicate the disease in humans exactly. Models are important in helping us understand the basic biology of the disease, but we need human studies in representative populations for ideas to be fully validated.”

Forner added that the Alzheimer’s Association is currently funding several studies investigating the impact of diet, diabetes, obesity, and neuroinflammation in the development of Alzheimer’s, dementia, and cognitive decline.

According to the National Institutes of Health, several studies have found that healthful diets, such as the Mediterranean, DASH, and MIND diets, may help to reduce the risk of Alzheimer’s disease.

This study adds further evidence that limiting fat intake may be beneficial for cognitive function, although more research is needed to determine whether the mechanisms seen in mice also apply to people.

Forner emphasized that to “understand the impacts and outcomes of a high-fat diet on people living with, or at risk for, Alzheimer’s,” studies in people are essential.

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