Brain Insulin Resistance as a Possible Link Between Alzheimer's Disease and Epilepsy

Recent research conducted by the University of São Paulo (USP) in Brazil suggests that insulin resistance within the brain may play a significant role in the development and progression of both Alzheimer's disease and epilepsy. Using animal models, scientists demonstrated that impaired insulin signaling in the brain affects neural health, contributing to neurodegeneration and increasing seizure susceptibility.

The study aligns with clinical observations that individuals with epilepsy are at a heightened risk of developing Alzheimer's disease as they age, and vice versa. It emphasizes that disruptions in insulin pathways in the brain – sometimes referred to as 'type 3 diabetes' – may be a crucial underlying factor linking these neurodegenerative and epileptic conditions.

In the experiments, rats injected with streptozotocin—a chemical used to model insulin resistance and Alzheimer’s disease—showed not only typical signs of memory impairment but also seizure-like behaviors. Interestingly, epileptic rats displayed molecular features characteristic of Alzheimer’s, such as tau protein hyperphosphorylation and decreased insulin receptors in critical brain regions like the hippocampus.

The findings suggest that insulin resistance in the brain can exacerbate memory deficits and seizure severity. The researchers also observed that brain insulin resistance could impair cholinergic transmission, promote neuroinflammation, and accelerate neuronal damage. This hypothesis supports the notion that Alzheimer’s disease may involve a form of brain-specific diabetes, termed 'type 3 diabetes,' highlighting the metabolic aspect of its pathology.

Furthermore, the study demonstrates that systemic conditions like diabetes increase Alzheimer’s risk, but central insulin resistance can occur independently of diabetes diagnosis. This broadens the understanding of disease mechanisms and points to the importance of metabolic health for brain function.

The research also uncovered that animals genetically predisposed to epilepsy exhibited Alzheimer-like molecular changes when subjected to insulin resistance, further reinforcing the link between these diseases. The work is part of an ongoing project that has received awards and recognition for its innovative approach.

The scientists further revealed that injecting insulin-resistant-inducing agents into epileptic animals worsened their cognitive and seizure profiles. They noted increased neuronal activity in insulin receptor-rich brain areas, strengthening the idea that insulin signaling pathways are critical in modulating neural excitability.

This pioneering research underscores the need for a broader therapeutic strategy targeting metabolic pathways in neurological disorders. It also encourages future studies involving human tissues and surgical samples to better understand how insulin resistance contributes to epilepsy and Alzheimer’s disease. The goal is to develop interventions that can modify insulin signaling in the brain, potentially preventing or slowing the progression of these devastating conditions.

Source: https://medicalxpress.com/news/2025-05-insulin-resistance-brain-factors-linking.html