Alterations in content and phosphorylation state of cytoskeletal proteins in the sciatic nerve during ageing and in Alzheimer's disease.

Abstract

Paired helical filaments containing the microtubule-associated protein tau in an abnormally high phosphorylated state are one of the major hallmarks of Alzheimer's disease. In the central nervous system, this neurofibrillar degeneration preferentially affects long-axon projection neurons. In the peripheral nervous system largely made up by long-axon neurons, formation of paired helical filaments, however, has only rarely been described. In the present study, we have analysed alterations in the content and phosphorylation state of tau and neurofilament protein in the sciatic nerve during ageing and in Alzheimer's disease. The amount of both cytoskeletal proteins remained constant during ageing but was significantly reduced in Alzheimer's disease. The phosphorylation state of tau protein was elevated during ageing as well as in Alzheimer's disease. No indications of a paired helical filament-like aggregation of tau were found. It is concluded that during normal ageing and in Alzheimer's disease, processes are activated in the peripheral nervous system that induce a hyperphosphorylation of tau. Increased phosphorylation of tau in peripheral neurons, however, is not necessarily accompanied by the formation of paired helical filaments. Analysing principal differences in the expression, posttranslational modification and metabolism of tau between central and peripheral neurons might, therefore, help to get a better insight into the mechanism of paired helical filament formation.