Whereas early reports on extracellular S100B supported the possibility that the protein might function as a trophic factor towards neurons and astrocytes [10], the observation that elevated levels of S100B were present in the temporal lobe of patients with Alzheimer disease in conjunction with the presence of highly reactive S100B-positive astrocytes surrounding the neuritic plaques [57] raised the possibility that S100B might contribute to Alzheimer disease neuropathology. This evidence concerns the gene S100B and early-onset autosomal dominant Alzheimer disease.