title: Progranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation Carriers.
abstract: BACKGROUND
  Pathogenic mutations in the granulin gene(GRN)are causative in 5-10% of patients with frontotemporal dementia (FTD), mostly leading to reduced progranulin protein (PGRN) levels. Upcoming therapeutic trials focus on enhancing PGRN levels.
  
  
  METHODS
  Fluctuations in plasma PGRN (n = 41) and its relationship with cerebrospinal fluid (CSF, n = 32) and specific single nucleotide polymorphisms were investigated in pre- and symptomaticGRNmutation carriers and controls.
  
  
  RESULTS
  Plasma PGRN levels were lower in carriers than in controls and showed a mean coefficient of variation of 5.3% in carriers over 1 week. Although plasma PGRN correlated with CSF PGRN in carriers (r = 0.54, p = 0.02), plasma only explained 29% of the variability in CSF PGRN. rs5848, rs646776 and rs1990622 genotypes only partly explained the variability of PGRN levels between subjects.
  
  
  CONCLUSIONS
  Plasma PGRN is relatively stable over 1 week and therefore seems suitable for treatment monitoring of PGRN-enhancing agents. Since plasma PGRN only moderately correlated with CSF PGRN, CSF sampling will additionally be needed in therapeutic trials.
authors.affiliation: Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Lieke H H
authors.initials: LH
authors.lastname: Meeter
authors.affiliation: Department of FORUM Pharmaceuticals Inc., Waltham, Mass., USA.
authors.forename: Holger
authors.initials: H
authors.lastname: Patzke
authors.affiliation: Department of FORUM Pharmaceuticals Inc., Waltham, Mass., USA.
authors.forename: Gordon
authors.initials: G
authors.lastname: Loewen
authors.affiliation: Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Elise G P
authors.initials: EG
authors.lastname: Dopper
authors.affiliation: Department of Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors.forename: Yolande A L
authors.initials: YA
authors.lastname: Pijnenburg
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Rick
authors.initials: R
authors.lastname: van Minkelen
authors.affiliation: Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: John C
authors.initials: JC
authors.lastname: van Swieten
keywords: Biomarker; Cerebrospinal fluid; Frontotemporal dementia; Granulin gene (GRN); Plasma; Progranulin protein; Single nucleotide polymorphism