Editorial: Brain Insulin Resistance in Neurodevelopmental and Neurodegenerative Disorders: Mind the Gap!
Mara Dierssen, Eugenio Barone
Abstract
or autism Specifically, regarding ADRDs and T2DM, considerable overlap has been found in the risk factors, comorbidities and putative pathophysiological mechanisms, leading to the proposal that AD is type 3 diabetes Examination of postmortem AD, amnestic mild cognitive impairment and DS brains, uncovered key signs of brain insulin resistance, i.e., reduced insulin receptor (IR) and increased serine phosphorylation (inhibitory) of insulin receptor substrate 1 (IRS1), as well as reduced activation of pathways downstream from IRS1, particularly in the hippocampus, cortex, and hypothalamus Higher levels of insulin resistance markers are associated with poorer performance on cognitive tests of episodic and working memory, independent of the load of senile plaques and tangles, thus suggesting a role for insulin signaling in neuronal functions At the cellular level, these dysfunctions might manifest as the impairment of neuroplasticity, receptor regulation or neurotransmitter release in neurons (Spinelli et al.,