Polyubiquitination of Tau Increases Across Braak Stages in Alzheimer’s Disease

The proteolytic ubiquitin‐proteasome system (UPS) is a main control mechanism of tau degradation in eukaryotic cells. Although the UPS is an integral regulator for tau turnover in healthy neurons, preliminary data suggests that the pathological tau in Alzheimer’s Disease (AD) is polyubiquitinated. This is an intriguing conundrum where the polyubiquitinylation of tau does not result in the degradation of the protein by the UPS. This suggests that the capacity of the UPS is limited or that the UPS is unable to degrade this form of tau. In this study, we aim to validate this potential correlation between the polyubiquitination of tau and AD, which could perhaps provide more clarity on the specific mechanisms of toxicity for AD.