The role of insulin resistance in MCI and dementia Insulin and insulin resistance play important roles and functions in the central nervous system and the development of age-related neurodegenerative diseases, including glucose metabolism, vascular function, synaptic maintenance, beta-amyloid regulation, and tau phosphorylation. Insulin is transported across the blood-brain barrier, and brain insulin receptors are selectively localized in key brain regions, such as hippocampus, entorhinal cortex, and frontal cortex, where it plays a direct role in modulating levels of important neurotransmitters, synaptic plasticity, learning and memory. Insulin has also been shown to regulate the metabolism of beta-amyloid and tau, the building blocks of amyloid plaques and neurofibrillary tangles which are the neuropathological hallmarks of AD. Peripheral hyperinsulinemia promotes oxidative stress, protein glycosylation and cerebral ischemia and impairs the clearance of amyloid beta in the brain through competition for insulin degrading enzyme (IDE).