Discovery could affect the search for new drugs for Alzheimer’s disease

Alzheimer’s disease is associated with reduced insulin receptors in brain microvessels, which may contribute to brain insulin resistance and the formation of amyloid plaques, one of the hallmarks of the disease. This is according to a study published today in a scientific journal Brain by a team from Laval University and Rush University Medical Center in Chicago.

The work leading to the discovery was led by Frédéric Calon, professor at the Faculty of Pharmacy and researcher at the Institute of Nutrition and Functional Foods and the Research Center of the CHU de Québec–Université Laval.

The results could affect the search for new drugs against Alzheimer’s disease.

Several clinical trials are underway to assess the effectiveness of diabetes medications in Alzheimer’s disease. Our study shows that drugs do not need to cross the blood-brain barrier of microvessels to affect insulin resistance in the brain. Instead, they can target insulin receptors located in brain microvessels. This expands the range of drugs that could be tested for Alzheimer’s disease.”

Frédéric Calon, Full Professor, Faculty of Pharmacy and Researcher, Institute of Nutrition and Functional Foods and Research Center of the CHU de Québec–Université Laval

The research was made possible by a longitudinal study that began in 1993 and involves approximately 1,100 members of some 30 religious congregations in the United States. The participants agreed to submit to annual medical and psychological tests and to donate their brains after their death. The Brain The article is based on data from 60 deceased people who participated in this in-depth study.

Examination of their brain revealed that:

  • Insulin receptors are found primarily in microblood vessels, not in neurons as previously thought.
  • Insulin receptor alpha-B subunits were less prevalent in the microvessels of people diagnosed with Alzheimer’s disease.
  • Cognitive test scores were lower in subjects with fewer alpha-B insulin receptors in their microvessels.
  • Subjects with fewer alpha-B insulin receptors in their microvessels had more beta-amyloid plaques in their brains.

Experiments conducted by the researchers on transgenic mice used to study Alzheimer’s disease showed that the amount of alpha-B receptors in the microvessels decreased with age and disease progression.

“Our results suggest that the loss of alpha-B insulin receptors in brain microvessels contributes to brain insulin resistance and cognitive decline in people with Alzheimer’s disease,” the researcher said. Professor Callon.

These results support the idea that Alzheimer’s disease is a neurodegenerative disease with a strong metabolic component. “Metabolic dysfunction exacerbates Alzheimer’s disease, and Alzheimer’s disease amplifies the metabolic problem. It’s a vicious cycle,” Professor Calon said.

The authors of the study are Manon Leclerc, Philippe Bourassa, Cynthia Tremblay, Vicky Caron, Camille Sugère, Vincent Emond and Frédéric Calon of Laval University, and David Bennett of Rush University Medical Center. This work was supported by the Canadian Institutes of Health Research (CIHR).

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