The β-amyloid peptide (Aß) is a 4 kDa proteolytic fragment derived from the β-amyloid precursor protein (βAPP) which is deposited as amyloid fibrils in the brains of patients with Alzheimer's disease. βAPP 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 Aß (1–40) and is specifically recognized by antibodies raised against N- or C-terminal domains of the β-amyloid peptide. Our results further suggest that glial cells may prove a major source of β-amyloid production in the nervous tissue.
