Insulin resistance linked to risk of developing Alzheimer’s disease

A URV-led research team has identified molecules in the blood that link insulin resistance to an increased risk of developing Alzheimer’s disease. The molecules are a type of metabolite, that is, compounds produced by a set of chemical reactions that occur in living organisms, and their discovery may improve current methods for predicting Alzheimer’s disease. “We have opened up a new avenue in research into the prevention and treatment of this disease and its relationship with metabolic diseases such as obesity,” explained Mónica Bulló, a researcher in the URV’s Department of Biochemistry and Biotechnology.

Alzheimer’s is an incurable, degenerative and terminal disease that is usually diagnosed in people over the age of 65. In the early stages, the characteristic symptom is memory loss. As the disease progresses, confusion, irritability, mood swings and loss of sensation appear. Finally, vital functions decline, ultimately leading to the patient’s death. According to the World Health Organisation, Alzheimer’s is the most common form of dementia, being diagnosed in more than 60 out of every 100 cases of dementia, and it is estimated to have an annual economic impact of approximately €1.2 billion worldwide.

Researchers from the Nutrition and Metabolic Health (NuMeH) research group worked with data from 400 individuals with mild cognitive impairment, who they followed for four years. During this period, impairment in 142 of the individuals progressed to dementia of the Alzheimer’s type. By analysing more than 600 plasma metabolites, extracted from the individuals’ blood during medical follow-up, they identified a set of 18 metabolites already associated with insulin resistance. “The fact that we have found biomarkers that coincide in these two pathologies paves the way for the early diagnosis of Alzheimer’s disease in insulin-resistant people, because metabolic dysfunction appears before cognitive symptoms,” explains Bulló.

In addition to improving the tools used for predicting Alzheimer’s, another positive aspect of the methods developed in this research is that they analyse metabolites in blood samples, which are easier to obtain than cerebrospinal fluid samples, where the patient has to undergo a much more invasive lumbar puncture.

A better understanding of the role that these molecules play in the earlier stages of the disease may also help in the design of new preventive and therapeutic strategies to slow the progression of Alzheimer’s disease and improve patients’ quality of life. Further knowledge of these compounds may also improve the treatments available for other pathologies with common metabolites, such as insulin resistance, which is common in patients with type 2 diabetes or obesity.

The research has been led by Professor Mónica Bulló, director of the NuMeH research group and the TecnATox centre, in collaboration with researchers from the Pere Virgili Health Research Institute, the Ace Alzheimer Centre in Barcelona, the Pablo de Olavide University in Seville and the URV’s ITAKA research group, also part of TecnATox.

Reference: Laia Gutierrez-Tordera, Laura Panisello, Pablo García-Gonzalez, Agustín Ruiz, José Luis Cantero, Melina Rojas-Criollo, Muhammad Mursil, Mercedes Atienza, Nil Novau-Ferré, Javier Mateu-Fabregat, Hamza Mostafa, Domènec Puig, Jaume Folch, Hatem Rashwan, Marta Marquié, Mercè Boada, Christopher Papandreou, Mònica Bulló, Metabolic signature of insulin resistance and risk of Alzheimer’s disease, The Journals of Gerontology: Series A, 2024;, glae283 https://doi.org/10.1093/gerona/glae283