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

Paired helical filaments containing the microtubule-associated protein tau in an abnormally high phosphorylated state are one of the major hallmarks o f Alzheimer's disease. In the central nervous system, this neurofibrillar d egeneration preferentially affects long-axon projection neurons. In the per ipheral nervous system largely made up by long-axon neurons, formation of p aired helical filaments, however, has only rarely been described. In the pr esent study, we have analysed alterations in the content and phosphorylatio n state of tau and neurofilament protein in the sciatic nerve during ageing and in Alzheimer's disease. The amount of both cytoskeletal proteins remai ned constant during ageing but was significantly reduced in Alzheimer's dis ease. The phosphorylation state of tau protein was elevated during ageing a s well as in Alzheimer's disease. No indications of a paired helical filame nt-like aggregation of tau were found. It is concluded that during normal a geing and in Alzheimer's disease, processes are activated in the peripheral nervous system that induce a hyperphosphorylation of tau. Increased phosph orylation of tau in peripheral neurons, however, is not necessarily accompa nied by the formation of paired helical filaments. Analysing principal diff erences 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.