The confirming diagnosis of Alzheimer's disease includes an assessment of the concentration of neuritic plaques in the temporal lobe of the brain. The presence of abnormal levels of neurotrophic factors in Alzheimer's disease is one possible explanation for the increased concentration of aggregates of overgrown neurites in the neuritic plaques of Alzheimer's disease. The protein S100 beta, a neurotrophic factor produced by astroglia in the brain, induces neurite outgrowth in cerebral cortical neurons. The generation of specific S100 beta antibodies, the cloning of a full-length cDNA encoding the S100 beta mRNA, and the development of a neurite extension assay system for S100 beta allowed testing of the hypothesis that Alzheimer's disease S100 beta expression is elevated in brain temporal lobe where neuritic plaques are concentrated. The levels of S100 beta protein, mRNA, and specific neurotrophic activity were elevated 10-20-fold in extracts of temporal lobe from autopsy samples of Alzheimer's disease patients compared to those of aged control patients. The cells containing the increased S100 beta were reactive astrocytes; the neuritic plaques were surrounded by S100 beta-containing astrocytes. The elevated levels of S100 beta provides a link between the prominent reactive gliosis and neuritic plaque formation in this common disease of the elderly and raises the possibility that S100 beta contributes to Alzheimer's disease neuropathology.