High-Resolution Magic Angle Spinning NMR of the Neuronal Tau Protein Integrated in Alzheimer's-Like Paired Helical Fragments

摘要

The intraneuronal accumulation of aggregates of the microtubule binding tau protein is together with the extracellular occurrence of beta-amyloid plaques the main molecular hallmark of Alzheimer's disease (AD).The in vivo origin of the aggregation process is not precisely known,although Abeta accumulation might trigger caspase-cleavage of tau,leading to hyperphosphorylation in the evolution of AD tangle pathology.Importantly,in vivo aggregated tau is mostly found in its hyperphosphorylated form.In vitro,however,the addition of polyanions such as heparin,heparan sulfate,arachidonic acid,or RNA can aggregate tau into filaments that appear as straight or paired helical filaments (PHFs) under electron microscopy similar to those isolated from diseased brain tissue.