Progranulin plasma levels predict the presence of GRN mutations in asymptomatic subjects and do not correlate with brain atrophy: results from the GENFI study

Neurobiol Aging. 2018 Feb:62:245.e9-245.e12. doi: 10.1016/j.neurobiolaging.2017.10.016. Epub 2017 Nov 13.


We investigated whether progranulin plasma levels are predictors of the presence of progranulin gene (GRN) null mutations or of the development of symptoms in asymptomatic at risk members participating in the Genetic Frontotemporal Dementia Initiative, including 19 patients, 64 asymptomatic carriers, and 77 noncarriers. In addition, we evaluated a possible role of TMEM106B rs1990622 as a genetic modifier and correlated progranulin plasma levels and gray-matter atrophy. Plasma progranulin mean ± SD plasma levels in patients and asymptomatic carriers were significantly decreased compared with noncarriers (30.5 ± 13.0 and 27.7 ± 7.5 versus 99.6 ± 24.8 ng/mL, p < 0.00001). Considering the threshold of >61.55 ng/mL, the test had a sensitivity of 98.8% and a specificity of 97.5% in predicting the presence of a mutation, independent of symptoms. No correlations were found between progranulin plasma levels and age, years from average age at onset in each family, or TMEM106B rs1990622 genotype (p > 0.05). Plasma progranulin levels did not correlate with brain atrophy. Plasma progranulin levels predict the presence of GRN null mutations independent of proximity to symptoms and brain atrophy.

Keywords: Biomarker; Brain atrophy; Frontotemporal dementia (FTD); Plasma levels; Progranulin (GRN); Proximity marker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Atrophy / genetics
  • Cohort Studies
  • Female
  • Frontotemporal Dementia / genetics*
  • Genetic Association Studies
  • Genetic Testing / methods
  • Gray Matter / pathology
  • Heterozygote
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood*
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Multicenter Studies as Topic
  • Mutation*
  • Nerve Tissue Proteins / genetics
  • Progranulins
  • Sensitivity and Specificity
  • Young Adult


  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Progranulins
  • TMEM106B protein, human