Mitosis of Schwann cells and demyelination are induced by the amyloid precursor protein and other protease inhibitors in the rat sciatic nerve.

We studied the cytological alterations produced in the rat sciatic nerve by the amyloid precursor protein (APP) containing the Kunitz insert (APP K+) and other protease inhibitors. Conditioning of nerve segments with APP K+, aprotinin or leupeptin for 5 days or more resulted in mitosis of Schwann cells, demyelination of fibres, and a < 10-fold increase in Schwann cells, associated with demyelinated fibres. Altered fibres nevertheless involved a small part of the population. Nerve segments proximal and distal to the conditioned region showed almost no alteration. Conditioning with saline, heated APP K+, or APP without the Kunitz insert was not effective. We conclude that APP K+ and other protease inhibitors induce Schwann cells to enter the cell cycle, and once committed to proliferate they resorb their myelin. These functional properties of APP may be relevant to the pathogenesis of Alzheimer's disease.