Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17

Abstract summary

Co-discovered with Cruts et al. that heterozygous loss-of-function mutations in GRN (progranulin) cause frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U). Progranulin is a pleiotropic growth factor expressed highly in microglia, and haploinsufficiency causes neuroinflammation and lysosomal dysfunction.

Evidence labels

Therapeutic relevance

Established GRN haploinsufficiency as the mechanism of FTD; recombinant progranulin replacement and GRN gene therapy are in clinical development.