Does insulin dysfunction play a role in Alzheimer's disease?

Age-related changes in hormone levels are determinants of a variety of human diseases. Insulin is known to affect numerous brain functions including cognition and memory, and several clinical studies have established links between Alzheimer's disease (AD), insulin resistance and diabetes mellitus. These are reinforced by biological studies that reveal the effects of insulin on the molecular and cellular mechanisms that underlie the pathology of AD. For example, insulin regulates phosphorylation of tau protein, which underlies neurofibrillary lesions in the brains of AD patients. Insulin also affects the metabolism of β-amyloid, the main constituent of AD amyloid pathology. Here, we discuss clinical and biological data that highlight potential targets for therapeutic intervention. In the CNS, insulin acts to regulate the phosphorylation of tau and modulate the metabolism of beta-amyloid precursor protein and beta-amyloid. These effects might account for the cognitive deficits and increased risk of developing Alzheimer's disease that are associated with types 1 and 2 diabetes.