The role of activated astrocytes and of the neurotrophic cytokine S100B in the pathogenesis of Alzheimer's disease.
Activated astrocytes, overexpressing the neurotrophic signaling molecule S100beta, are invariant components of the Abeta plaques of Alzheimer's disease. Even early, nonfibrillar amyloid deposits in Alzheimer's disease contain such astrocytes, and the numbers and degree of activation of these wax and wane with the subsequent neuritic pathology of plaque evolution. Astrocytic overexpression of S100B in the neuritic plaques of Alzheimer's disease correlates with the degree of neuritic pathology in Abeta plaques in this disease, suggesting a pathogenic role for S100B's neurotrophic properties in the evolution of these lesions. Astrocytic overexpression of S100B, in turn, is promoted by high levels of interleukin-1 (IL-1), originating from activated microglia that are also constant components of Abeta plaques in Alzheimer's disease. Similar patterns of astrocyte activation, S100B overexpression, microglial activation, and IL-1 overexpression are seen in conditions that confer risk for Alzheimer's disease (aging, head trauma, Down's syndrome), in conditions that predispose to accelerated appearance of Alzheimer-like neuropathologic changes (chronic epilepsy, HIV infection), and in animal models of Alzheimer's disease. These cells and molecules are an important components of a cytokine cycle of molecular and cellular cascades that may drive disease progression in Alzheimer's disease.
Mrak
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Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. mrakroberte@uams.edu
Griffinbc
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D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D009418:S100 Proteins / Q000096:biosynthesis / Q000502:physiology*
D016207:Cytokines; D009418:S100 Proteins