Mind the Metabolic Gap: Bridging Migraine and Alzheimer's disease through Brain Insulin Resistance.

Brain insulin resistance has recently been described as a metabolic abnormality of brain glucose homeostasis that has been proven to downregulate insulin receptors, both in astrocytes and neurons, triggering a reduction in glucose uptake and glycogen synthesis. This condition may generate a mismatch between brain's energy reserve and expenditure, ??mainly during high metabolic demand, which could be involved in the chronification of migraine and, in the long run, at least in certain subsets of patients, in the prodromic phase of Alzheimer's disease, along a putative metabolic physiopathological continuum. Indeed, the persistent disruption of glucose homeostasis and energy supply to neurons may eventually impair protein folding, an energy-requiring process, promoting pathological changes in Alzheimer's disease, such as amyloid-β deposition and tau hyperphosphorylation.

Migraine, Brain Glucose Metabolism and the "Neuroenergetic" Hypothesis: A Scoping Review.

Increasing evidence suggests that migraine may be the result of an impaired brain glucose metabolism. Several studies have reported brain mitochondrial dysfunction, impaired brain glucose metabolism and gray matter volume reduction in specific brain areas of migraineurs. Furthermore, peripheral insulin resistance, a condition demonstrated in several studies, may extend to the brain, leading to brain insulin resistance.