Immune attack: the role of inflammation in Alzheimer disease

It is now emerging that the neuroinflammation that is associated with Alzheimer disease may have a key role in driving this disease. In this Review, Heppner, Ransohoff and Becher examine the contribution of the immune system to the pathogenesis of this disorder. The past two decades of research into the pathogenesis of Alzheimer disease (AD) have been driven largely by the amyloid hypothesis; the neuroinflammation that is associated with AD has been assumed to be merely a response to pathophysiological events. However, new data from preclinical and clinical studies have established that immune system-mediated actions in fact contribute to and drive AD pathogenesis. These insights have suggested both novel and well-defined potential therapeutic targets for AD, including microglia and several cytokines. In addition, as inflammation in AD primarily concerns the innate immune system — unlike in 'typical' neuroinflammatory diseases such as multiple sclerosis and encephalitides — the concept of neuroinflammation in AD may need refinement.