Alzheimer’s disease is related to a discount of insulin receptors in brain microvessels, which can contribute to brain insulin resistance and the formation of amyloid plaques, certainly one of the disease’s hallmarks. That is in response to a study published today in scientific journal Brain by a team from Université Laval and Rush University Medical Center in Chicago.

The work resulting in the invention was headed by Frédéric Calon, a professor on the Faculty of Pharmacy and a researcher on the Institute of Nutrition and Functional Foods and the CHU de Québec–Université Laval Research Centre.

The findings could affect the search for brand spanking new Alzheimer’s drugs.

Several clinical trials are underway to evaluate the efficacy of diabetes drugs for Alzheimer’s disease. Our study shows that drugs don’t have to cross the blood–brain barrier of microvessels to affect brain insulin resistance. As a substitute, they’ll goal insulin receptors positioned in cerebral microvessels. That expands the range of medication that could possibly be tested for Alzheimer’s.”

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

The research was made possible by a longitudinal study that began in 1993 and involves about 1,100 members of some 30 religious congregations in america. The participants have agreed to undergo annual medical and psychological tests and donate their brains after death. The Brain article is predicated on data from 60 deceased individuals who participated on this extensive study.

Examination of their brains revealed that:

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

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

“Our findings suggest that the lack of alpha-B insulin receptors in brain microvessels contributes to insulin resistance within the brain and cognitive decline in individuals with Alzheimer’s disease,” Professor Calon said.

These findings support the concept that Alzheimer’s is a neurodegenerative disease with a powerful metabolic component. “Metabolic dysfunction exacerbates Alzheimer’s, and Alzheimer’s amplifies the metabolic problem. It is a vicious circle,” said Professor Calon.

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