Neuroinflammatory processes in the pathogenesis of Alzheimer's disease

Alzheimer's disease (AD), which is characterized by a progressive decline in memory and other cognitive functions, is the most common dementia in today's society. The incidence of this condition is on the rise, and currently there are no effective treatment modalities. Microglia-mediated neuroinflammation is thought to be associated with the initiation and progression of a number of neurodegenerative conditions including AD. Chronic activation of microglia exposes the central nervous system to various cytokines, chemokines, complement proteins, reactive oxygen species, all of which could have neurotoxic consequences when present in excess. In the neuroinflammatory foci of Alzheimer's the neurofibrillary tangles and Aß aggregates are associated with activated microglia and increased levels of a purinergic P2X7 receptor (P2X7R). We have shown that up-regulation of P2X7R is sufficient to drive the activation and proliferation of microglia, as well as enhancing the release of various inflammatory mediators. This chapter will highlight some of the recent findings in the field of Alzheimer's research of particular reference to the neuroinflammatory hypothesis. The contribution to AD progression of immunomodulatory responses such as microglial activation, and the role of P2X7R, will be discussed.