糖代謝異常からみたAlzheimer病

抄録

Alzheimer's disease (AD) is the most common cause of dementia in adult in Japan. In AD brain, two types of pathological findings including extracellular amyloid–β deposition and intracellular phosphorylated tau accumulation are observed. Although symptomatic therapy using choline esterase inhibitor and/or memantine are available for patients with AD, no effective disease–modifying drugs that may ameliorate natural history of AD has not currently established. AD is now recognized as one of largest unmet medical need among physicians. Thus, new therapeutic targets for drugs showing the disease modifying effect need to be explored. Epidemiological studies have shown that type 2 diabetes mellitus (T2DM) is associated with a nearly two–fold increased risk of AD. Although precise mechanisms of linking T2DM and AD remains unknown, accumulating evidence suggests that insulin resistance in brain plays a pivotal role in the pathogenesis of AD. This review article focuses on molecular aspect and the pharmacological strategies from the view of insulin resistance occurring in AD brain.