Researchers at the University of Sao Paulo (USP) in Brazil have been able to show, in a animal model, that the process of insulin resistance to the brain affects both Alzheimer’s disease and epilepsy and may be a factor in connection between the two diseases.
The project, supported by FAPESP, confirms clinical evidence that people with epilepsy are at greater risk of developing Alzheimer’s disease as they grow older. It is also not uncommon for people with Alzheimer’s disease having epileptic seizures.
“In addition to proof that insulin signaling in the brain, when changing, affects both epilepsy and Alzheimer’s disease, the study enhances the idea that Alzheimer’s disease is even more complex and therefore requires a wider treatment approach. Neurophysiology and Experimental Neuroshemology and a corresponding author of the article published in The Newspaper of nervous transmission.
Alzheimer’s disease is a complex, multifactorial neurodegenerative disease for which there is no treatment and no known cause. Among the various cases to explain its appearance, the amyloid waterfall stands out, according to which the deposition of beta-amyloid plaques in the brain is the initial and critical event that activates a series of processes that culminate in neuronal death, loss of synods.
It was formulated in 1992, this theory has guided Alzheimer’s research for recent decades.
Other important cases include a decrease in acetylcholine, a neurotransmitter necessary for memory, and neurofemation, which prevents communication between neurons and can be activated by the accumulation of amyloid peptides in the brain. In addition, the hyperphosphation of the Tau protein, the second main biomarker of Alzheimer’s disease, leads to the formation of “confused” in brain cells, reducing their function and contributing to the progression of the disease.
“Currently, the drugs commonly used to treat Alzheimer’s [anticholinesterase and antiglutamatergic drugs] They have low efficiency and are only symptomatic. And cases of people with beta-amyloid plates in the brain [the result of the deposition of amyloid peptides] Without Alzheimer’s symptoms they have already been described, “the researcher says.
Metabolic nature
Another hypothesis to explain the appearance of Alzheimer’s, highlighted by Garcia-Cairarasco, is that the process of brain resistance to insulin leads to neuronal damage and defective synaptic plasticity in an area of ​​the hippocampus brain. Resistance to brain insulin could even harm cholinergic function, increasing the likelihood of neurofemlamis and neurodegeneration and activating beta-amloid and tau protein in brain tissue.
It is worth noting that although patients with diabetes have a higher risk of Alzheimer’s, there may be central insulin resistance without having type 1 or type 2 diabetes.
According to this case, which is not yet consensus between experts, Alzheimer’s will be due to a type of diabetes called type 3, which describes a state of resistance to insulin in the brain.
Epilepsy, on the other hand, is a group of disorders characterized by recurrent and spontaneous crises (jerk or non -exhaustive), with a higher prevalence in children and older adults. Among the various factors that cause seizures are low blood sugar (hypoglycaemia). The cause of the disease may also be genetic or may be associated with brain trauma, autoimmune disorders, metabolic problems and infectious diseases.
There are scientists who exclusively associate Alzheimer’s with neurofemis, changes in neurotransmitters or type 3 diabetes. We believe that Alzheimer’s can be classified as a much more complex disease and that deeper understanding of its relationship with epilepsy and resistance to our relationship and resistance.
Norberto Garcia-Cairarasco, Professor at Ribeirão Preto Medical School (FMRP-TH)
The study is one of the first to show an immediate relationship between insulin resistance to the brain and increased sensitivity to seizures. In addition, the project is part of a larger project that has already won two excellent scientific awards in 2024 Рthe Aristides Lẹo Award (the best paper in the base area) at the Brazilian Brazilian Congress of Brazilian Epilepsy and the Best Poster Award at Geriatrics, at the 12th Brazilian Alzheimer.
Looks like an epileptic seizure
To get to these results, FMRP-USP researchers found that the micro-established rats intravenously with streptozotocin-a chemical used to experimentally cause Alzheimer’s disease-also presented epilepsy.
“To test the case of type 3 diabetes in a animal model, we have injected rodents with streptozotocin, a compound known to cause insulin resistance and is used to model Alzheimer’s diabetes and disease. The laboratory, which provided for other researchers.
The opposite was also observed: Wistar Audogenic Rat (WAR) rats, genetically modified to study epilepsy, also began to present molecular changes in Alzheimer’s disease, such as TAU protein hyperphosphation and reduction of Insulin receptors.
A single dose of the drug that was injected into rodents with epilepsy and Alzheimer’s disease not only caused insulin brain resistance, but also aggravates the memory of rodents and increased the frequency and severity of seizures.
“In addition to memory deficits, we have found that this model has increased sensitivity to acoustic seizures, along with increased neuronal activation in areas of the brain rich in insulin receptors.
“In addition, the results observed in the war official emphasize the importance of the genetic background in shaping the treatment of treatment, suggesting that inherent characteristics can affect disorders in insulin signaling that affect the progress of the disease,” the researcher concludes.
It is worth noting that the Epilepsy Raw Executive and Alzheimer’s disease developed genetically on the FMRP-USP was donated to the Rat Center, Research and Research Center (RRRC) at the University of Missouri (United States), where it is available to researchers from all over the world.
Before bribed, the executive is fired at the Multidisciplinary Center for Biological Research in the field of Science in the Campinas State University of Science (UNICAMP) to overcome international health barriers.
The team continues to study the relationship between the two diseases. Through a study supported by FAPESP and conducted in collaboration with the FMRP-ASP School Hospital (CLÃnicas Hospital) of the General Hospital and School Hospital (CLÃnicas Hospital), it will reproduce the study performed in rats using tissues from treatment).
The change in gene expression and protein in these patients will also be analyzed using protein and transcriptional techniques in another collaboration with researchers from Harvard University in the United States.
Source:
Magazine report:
Alves, SS, et al. (2025). Insulin signaling disorder exacerbates memory impairment and sensitivity to seizures in an epilepsy model with Alzheimer’s disease -like pathology. Newspaper of nervous transmission. Doi.org/10.1007/S00702-025-02896-1.
