Degradation of Oligomer Tau by Autophagy

Abstract

AbstractBackgroundThe specific pathological findings in Alzheimer’s disease (AD) brain are senile plaques composed of amyloid‐β protein (Aβ) and neurofibrillary tangles (NFTs) composed of highly phosphorylated tau protein. It has been suggested that autophagy may play an important role in the degradation of tau proteins. In this study, we investigated whether autophagy is involved in the degradation of oligomeric tau by immunohistochemistry using autopsied AD brains.MethodFrozen brains were homogenized to produce lysates, and Western blotting (WB) was performed using anti‐LC3 antibody, a marker of autophagy. The parietal lobes of the same autopsy brains were used for immunohistochemical analysis using anti‐LC3, anti‐P62, anti‐oligomeric tau antibody (TOC‐1) and anti‐phosphorylated tau antibody (PHF‐1).ResultIn the WB of the temporal lobe, LC3‐II was generally increased in AD brains compared to controls. In addition, immunostaining showed that oligomeric tau (TOC1) and LC3 coexisted in AD brains. In AD and control brains, phosphorylated tau, which stained faintly, was found to coexist with LC3, but LC3 was not found in the cytoplasm of neurons with serious phosphorylated tau (PHF‐1) deposition. However, the coexistence of highly phosphorylated tau and p62 was remarkable. No LC3 or P62 staining was observed in the neuropil thread.ConclusionThese results suggest that oligomeric tau is degraded by autophagy and phosphorylated tau is also degraded by autophagy, but autophagy may no longer function when the degree of phosphorylated tau deposition is serious.