A Role for Calcineurin in Alzheimers Disease

Abstract

Alzheimer's disease (AD) is an incurable age-related neurodegenerative disorder characterized by profound memory dysfunction. This bellwether symptom suggests involvement of the hippocampus --a brain region responsible for memory formation --and coincidentally an area heavily burdened by hyperphosphorylated tau and neuritic plaques of amyloid beta (A). Recent evidence suggests that pre-fibrillar soluble A underlies an early, progressive loss of synapses that is a hallmark of AD. One of the downstream effects of soluble A aggregates is the activation of the phosphatase cal-cineurin (CaN). This review details the evidence of CaN hyperactivity in 'normal' aging, models of AD, and actual disease pathogenesis; elaborates on how this could manifest as memory impairment, neuroinflammation, hyperphosphorylated tau, and neuronal death.