A culture model for age-related human neurofibrillary pathology.

Cloned human neuroblastoma cells have been induced to differentiate with retinoic acid whereupon they form an extensive network of processes and pseudoganglia. Ultrastructural examination shows these processes often contain assembled neurofilaments arranged parallel to microtubules in orderly arrangements characteristic of normal neurons. Perturbation of these differentiated, ganglion like cells with agents such as aluminum, zinc, and possibly leupeptin results in apparent neurofibrillary pathologies as evidenced by neurofilament specific immunofluorescent microscopy. A quantitative increase in neurofilament-specific antibody binding induced by aluminum and leupeptin were verified by flow cytometry with a fluorescence activated cell sorter. The utility of this system in screening agents for their capacity to produce neurofibrillary lesions characteristic of age-related human disorders is discussed.