In addition, TDP-43 protein accumulates in FTLD caused by the loss-of-function of PGRN; this indicates a tight connection of PGRN to SG assembly and NDs because TDP-43 pathology has been observed in a spectrum of NDs, including FTLD-U, ALS, ALS–FTLD, AD, and Guam Parkinson dementia complex (reviewed in [83]). Here, GRN is linked to Alzheimer disease.