Sophie Robinson

This study shows that reduced progranulin leads to increased legumain activity, which promotes TDP-43 pathology in FTLD, suggesting legumain as a therapeutic target.

The paper identifies a microglial activity biomarker panel that differentiates FTD-GRN and AD cases from controls using proteomic analysis in mouse models and human samples.

Peripheral AAV-mediated delivery of brain-penetrant PGRN rescues TDP-43 pathology, neurodegeneration and motor phenotypes in FTLD-GRN models.

This study shows that TREM2 deficiency reduces microglial hyperactivation in GRN-deficient models but does not rescue lysosomal dysfunction or neurodegeneration biomarkers.