Human brain S100 beta and S100 beta mRNA expression increases with age: Pathogenic implications for Alzheimer's disease

S100 beta is a neurite extension factor that has been implicated in the development of neuritic plaques in Alzheimer's disease. We analyzed the expression of S100 beta and its encoding mRNA, using immunohistochemistry, enzyme-linked immunosorbent assay, and Northern blot analysis, in postmortem brain tissue from 26 neurologically normal patients, aged 1-80 years. Tissue levels of S100 beta and S100 beta mRNA, as well as the number of S100 beta-immunoreactive (S100 beta(+)) astrocytes, increased with advancing age (r = 0.60, p = 0.008; r = 0.65, p = 0.007; and r = 0.73, p = 0.001, respectively). In patients more than 60 years old, the number of S100 beta(+) astrocytes and the tissue levels of S100 beta and S100 beta mRNA were significantly higher than those in patients less than 60 years of age (p = 0.001, p = 0.035, and p = 0.047, respectively). All of these values, however, were significantly less than those found in Alzheimer patients (p < 0.05 or better). Our findings, together with the known functions of S100 beta, suggest that age-related increases in S100 beta expression are important in the pathogenesis of Alzheimer's disease and may explain in part the increased incidence of this disease with advancing age.