Immunological aspects of microglia: relevance to Alzheimer's disease.
Alzheimer's disease (AD) is a progressive dementing neurologic illness, and the most frequent cause of dementia in the elderly. Neuritic plaques are one of the main neuropathological findings in AD, and the major protein component is the beta-amyloid protein (A beta). Another striking feature of neuritic plaques is the presence of activated microglia, cytokines, and complement components, suggestive of "inflammatory foci" within AD brain. In this review, we will examine the mechanisms by which microglia become activated in AD, emphasizing the role in the A beta protein and proinflammatory cytokines. As well, pathways for suppression of microglial activation by immunosuppressive cytokines will be described. Inflammation mediated by activated microglia is an important component of AD pathophysiology, and strategies to control this response could provide new therapeutic approaches for the treatment of AD.
Benveniste
E N
EN
Department of Cell Biology, The University of Alabama at Birmingham, 1918 University Boulevard, MCLM 395, Birmingham, AL 35294-0005, USA. tika@uab.edu
Nguyen
V T
VT
O'Keefe
G M
GM
D000276:Adjuvants, Immunologic / Q000502:physiology; D000544:Alzheimer Disease / Q000503:physiopathology*; D000818:Animals; D019013:CD40 Antigens / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D015847:Interleukin-4 / Q000494:pharmacology; D017628:Microglia / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D019013:CD40 Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D016212:Transforming Growth Factor beta; D015847:Interleukin-4