Inflammation and neurodegenerative diseases

Abstract

The decline in mental fitness associated with Alzheimer disease is accompanied by physical changes in the brain, including the development of characteristic plaques and neurofibrillary tangles, but the pathogenesis of those changes is not clear. Recent work suggests that the activation of microglia in response to injury, illness, aging, or other causes begins a cascade of events that can best be characterized as an inflammatory process. This cascade is mediated at first by the proinflammatory cytokine interleukin 1, which is overexpressed by the activated microglia. Through various pathways, interleukin 1 causes neuronal death, which activates more microglia, which in turn release more interleukin 1 in a self-sustaining and self-amplifying fashion. Over a period of years, this slow, smoldering inflammation in the brain destroys sufficient neurons to cause the clinical signs of Alzheimer disease.