Amyloid-ß Effects on Peripheral Nerve: A New Model System.

ABSTRACT

Although there are many biochemical methods to measure amyloid-ß (Aß)42 concentration, one of the critical issues in the study of the effects of Aß42 on the nervous system is a simple physiological measurement. The in vitro rat sciatic nerve model is employed and the nerve action potential (NAP) is quantified with different stimuli while exposed to different concentrations of Aß42. Aß42 predominantly reduces the NAP amplitude with minimal effects on other parameters except at low stimulus currents and short inter-stimulus intervals. The effects of Aß42 are significantly concentration-dependent, with a maximum reduction in NAP amplitude at a concentration of 70 nM and smaller effects on the NAP amplitude at higher and lower concentrations. However, even physiologic concentrations in the range of 70 pM did reduce the NAP amplitude. The effects of Aß42 became maximal 5-8 h after exposure and did not reverse during a 30 min washout period. The in vitro rat sciatic nerve model is sensitive to the effects of physiologic concentrations of Aß42. These experiments suggest that the effect of Aß42 is a very complex function of concentration that may be the result of amyloid-related changes in membrane properties or sodium channels.