Tau degradation in Alzheimer's disease: Mechanisms and therapeutic opportunities.

55 Specifically, there is a significant decrease in soluble UCH‐L1 protein levels but an increasing trend of insoluble UCH‐L1 levels in AD frontal cortex, 58 and soluble UCH‐L1 protein levels are inversely proportional to NFTs numbers in AD frontal cortex. 55 A recent study also reported that UCH‐L1 protein levels decreased in the cerebral cortex (superior frontal gyrus) of patients with late‐onset sporadic AD. 57 Therefore, in different brain regions and stages of AD, the regulation of UPS might be different, and it is crucial to investigate whether these changes are due to gene expression, protein degradation, or aggregation.

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