• A study on the interaction of Alzheimer's disease beta amyloid protein with cultured mouse neuroblastoma cell line NB41A3

      Zhao, Xiaohong (1994)
      The $\beta$ amyloid protein is the primary constituent of amyloid plaques in the brains of Alzheimer's disease patients. The generation of $\beta$ amyloid protein from $\beta$ amyloid precursor protein and its interaction with neuronal cells were studied in the mouse neuroblastoma cell line NB41A3. Immunoreactivity to the carboxyl terminal of the precursor protein was detected among the membrane proteins of these cells, indicating that $\beta$ amyloid precursor protein is produced by NB41A3 cells. Also amyloid precursor protein carboxyl terminal immunoreactivity was observed in the conditioned medium of the cells, demonstrating various cytosolic peptide fragments are secreted during the cellular processing of the $\beta$ amyloid precursor protein. Synthetic $\beta$ amyloid peptide was shown to negatively affect NB41A3 neuroblastoma cells as judged by decreasing cell numbers, decreasing amount of cell protein, and release of the cytosolic enzyme, lactic dehydrogenase, into the medium. At the ultrastructural level, internal damage to the nucleus could be observed. Synthetic $\beta$ peptide showed specific binding with neuroblastoma cells. The internalization of the $\beta$ peptide into the cells suggest a direct mechanism for $\beta$ amyloid protein toxicity in vivo. This research contributes to the knowledge of the processing of Alzheimer's disease $\beta$ amyloid precursor protein in NB41A3 cells and demonstrates that NB41A3 cell provides a practical in vitro model for studying the mechanism of Alzheimer's disease and amyloid toxicity.