Protein Gelation around Axons Inhibits Action Potential Propagation inNerve Fibers

Recently, we reported that amyloid fibers can further aggregate and form gels. In this paper, we provide evidence that protein gels, when formed outside nerve fibers, can substantially reduce the compound action potential. Protein gelation also increases the viscosity of the media. The nerve fiber’s compound action potential was found to be inversely related to the concentration of glycerol applied extracellularly. Soluble oligomer aggregates and fibrils on the other hand had little effect on action potential. These results suggest that the formation of protein gels surrounding neuronal processes, as in the case of amyloid plaques of Alzheimer’s disease, may disrupt the propagation of action potential and then trigger a cascade of events leading to neuronal death. As illustrated in Darcy’s law, gels restrict fluid flow and then the circulation of ions and molecules, which might underlie the pathogenesis of Alzheimer’s disease.