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A harmful Tau mutation may cause problems in cell waste removal that reduce Tau breakdown in frontotemporal dementia
Updated
Abstract
Essence
A disease-causing MAPT p.R406W Tau mutation disrupted neuronal -lysosome clearance and limited Tau degradation.
Evidence
This human-neuron model used super-resolution imaging and pharmacologic autophagy enhancement to track Tau, lysosome function, cargo clearance, and Tau levels.
Caveat
The findings come from a cellular disease model, and boosting autophagy lowered Tau without restoring lysosomal motility defects.
Simplified
Key numbers
67.1%
Increase in lysosomes free of Tau
Percentage of lysosomes free of Tau in G2-567 treated p.R406W neurons.
37
Decrease in total Tau levels
Mean intensity of total Tau per cell in G2-567 treated p.R406W neurons.
56
Decrease in pTau levels
Mean intensity of pTau per cell in G2-567 treated p.R406W neurons.