Production of the Alzheimer's beta-amyloid peptide by C6 glioma cells.

ABSTRACT

The beta-amyloid peptide (A beta) is a 4 kDa proteolytic fragment derived from the beta-amyloid precursor protein (beta APP) which is deposited as amyloid fibrils in the brains of patients with Alzheimer's disease. beta APP processing was investigated in C6 glioma cells using several affinity-purified anti-peptide antibodies raised against different domains of the protein. Both direct immunoblot analysis of C6 glioma conditioned medium and metabolic labeling of cells followed by immunoprecipitation of extracellular medium with specific antibodies revealed that these glial cells normally produce and release a soluble 4 kDa peptide which co-migrates with synthetic A beta (1-40) and is specifically recognized by antibodies raised against N- or C-terminal domains of the beta-amyloid peptide. Our results further suggest that glial cells may prove a major source of beta-amyloid production in the nervous tissue.