A new study sheds light the potential mechanism linking a diet high in saturated fats to Alzheimer’s disease. Researchers have identified specific changes in small RNA molecules, known as microRNAs, that act as markers and regulators of the disease, shedding light on how dietary habits can influence the onset of neurodegenerative conditions. The findings were published in the journal Nutrients.
“The 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,” said researcher Mònica Bulló
Alzheimer’s disease is a progressive neurodegenerative disorder characterized by the gradual loss of cognitive functions, including memory, thinking, and reasoning skills. It is the most common cause of dementia among older adults. The disease typically begins with mild memory loss but can progress to severe impairment in communication, behavior, and the ability to carry out daily activities.
Key pathological features of Alzheimer’s include the accumulation of β-amyloid plaques and tau protein tangles in the brain, which disrupt neuronal function and lead to cell death. These changes are accompanied by inflammation and reduced brain volume, further contributing to cognitive decline.
Researchers conducted the new study to investigate the underlying mechanisms that link dietary habits, specifically a diet high in saturated fats, to the development of Alzheimer’s disease. Previous studies had established that metabolic conditions such as obesity and type 2 diabetes are significant risk factors for Alzheimer’s, with these conditions often preceding or exacerbating the onset of the disease.
However, the exact biological pathways connecting these metabolic disorders to Alzheimer’s were not well understood. By focusing on the role of microRNAs, small RNA molecules that regulate gene expression, the researchers aimed to uncover how dietary-induced metabolic changes could influence brain health and accelerate neurodegeneration.
The researchers were particularly interested in microRNAs related to insulin regulation and Alzheimer’s pathology. Insulin resistance, a common feature of obesity and type 2 diabetes, has been linked to the development of Alzheimer’s. By studying changes in microRNA levels in both the blood and brain tissues of mice on a high-fat diet, the researchers hoped to identify specific molecular markers that could explain the connection between a high-fat diet and Alzheimer’s.
The study was conducted using mouse models genetically predisposed to develop Alzheimer’s disease in adulthood. The researchers compared these mice to healthy wild-type mice, with both groups split into two dietary regimens: one with conventional chow and the other with a diet high in saturated fats. The high-fat diet, rich in palmitic acid from hydrogenated coconut oil, comprised 60% of the mice’s daily intake.
The mice were monitored over six months, during which their body weight, glucose tolerance, and insulin response were measured. Blood and brain tissue samples were collected at the end of the study to analyze the expression of 15 specific miRNAs. These miRNAs were chosen based on their known roles in insulin regulation and neurodegenerative processes.
The researchers observed that mice on a high-fat diet showed marked metabolic deterioration, including significant weight gain and impaired glucose and insulin responses. These metabolic changes are similar to those seen in conditions like obesity and type 2 diabetes, both of which are known risk factors for Alzheimer’s disease.
One of the key discoveries was the alteration in levels of specific microRNAs in both the blood and brain tissues of the mice. The study identified significant changes in the expression of 15 insulin-related microRNAs. Notably, miR-19a-3p was consistently upregulated in the blood, cortex, and hippocampus of mice on the high-fat diet. This consistent upregulation suggests that miR-19a-3p might play a pivotal role in linking peripheral metabolic disturbances to central neurodegenerative processes.
The researchers also found that the altered microRNAs were associated with key pathological processes of Alzheimer’s disease. These include the accumulation of β-amyloid plaques, the excessive production of tau protein, and increased brain inflammation.
For example, miR-29c-3p, another microRNA that was upregulated in the brain and blood of mice on the high-fat diet, is known to negatively regulate β-secretase (BACE1), an enzyme involved in the production of β-amyloid plaques. The upregulation of miR-29c-3p could be a counter-regulatory response to the high-fat diet’s harmful effects, aiming to mitigate the formation of these plaques.
The study highlighted the potential of microRNAs as biomarkers and therapeutic targets. The consistent changes in specific microRNAs across different tissues suggest that they could serve as early indicators of Alzheimer’s-related changes induced by dietary factors. This opens up possibilities for developing non-invasive diagnostic tools based on blood tests to detect early molecular signs of Alzheimer’s. Targeting these microRNAs through dietary interventions or pharmacological approaches could offer new strategies for preventing or slowing the progression of Alzheimer’s disease.
The study represents a significant step forward in understanding how dietary habits influence the risk of Alzheimer’s disease, but translating these results to humans requires additional studies. Clinical trials are necessary to confirm the role of these microRNAs in Alzheimer’s disease in human populations and to test potential dietary interventions.
“In summary, our findings support the role of specific insulin-related miRNAs in the development of Alzheimer’s specific features and indicate the potential of a high-fat diet to aggravate neurodegenerative processes. Notably, miR-19a-3p and miR-29c-3p showed similar variations in both peripheral and central levels after high-fat diet consumption, suggesting their potential role not only as therapeutic targets for Alzheimer’s disease but also as peripheral biomarkers of the disease,” the researchers concluded.
The study, “Effects of a High-Fat Diet on Insulin-Related miRNAs in Plasma and Brain Tissue in APPSwe/PS1dE9 and Wild-Type C57BL/6J Mice,” was authored by Melina Rojas-Criollo, Nil Novau-Ferré, Laia Gutierrez-Tordera, Miren Ettcheto, Jaume Folch, Christopher Papandreou, Laura Panisello, Amanda Cano, Hamza Mostafa, Javier Mateu-Fabregat, Marina Carrasco, Antoni Camins, and Mònica Bulló.