The impact of neuroimmune changes on development of amyloid pathology; relevance to Alzheimer's disease.

Abstract

Neuroinflammatory changes are a characteristic of several, if not all, neurodegenerative diseases including Alzheimer?s disease (AD) and are typified by increased microglial activation. Microglia express several receptors making them highly reactive and plastic cells, and, at least in vitro, they adopt different phenotypes in a manner analogous to their peripheral counterparts, macrophages. Microglia also express numerous cell surface proteins enabling them to interact with cells and the evidence indicates that maintenance of microglia in a quiescent state relies, at least to some extent, on an interaction with neurons by means of specific ligand-receptor pairs for example CD200-CD200R. It is clear that microglia also interact with T cells and recent evidence indicates that co-incubation of microglia with Th1 cells markedly increase their activation ? ? ? Under normal conditions, small numbers of activated T cells gain entry to the brain and are involved in immune surveillance but infiltration of significant numbers of T cells occurs in disease and following injury. The consequences of T cell infiltration appear to depend on the conditions, with descriptions of both neur odestructive and neuroprotective effects in animal models of different diseases. This review will discuss the modulatory effect of T cells on microglia and impact of infiltration of T cells into the brain with a focus on AD and will propose that infiltration of interferon (IFN)- ? -producing cells may be an important factor in triggering inflammation that is pathogenic and destructive