Proteomic analysis links truncated tau to lysosome motility, autophagy, and endo-lysosomal dysfunction.

In mouse brain samples, we observed a trend toward reduced cathepsin B activity in Tau35 compared to WT, most notably in lysosomal fractions at 10 months (45.3% reduction), although this did not reach statistical significance (Figure 5A ).

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Overall, cathepsin B activity showed a trend toward a reduction in Tau35 mouse brains but was significantly increased in tau‐overexpressing SH‐SY5Y cells, while cathepsin D activity remained largely unchanged in both systems.

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