title: Optimal plasma progranulin cutoff value for predicting null progranulin mutations in neurodegenerative diseases: a multicenter Italian study.
abstract: BACKGROUND
  Recently, attention was drawn to a role for progranulin in the central nervous system with the identification of mutations in the progranulin gene (GRN) as an important cause of frontotemporal lobar degeneration. GRN mutations are associated with a strong reduction of circulating progranulin and widely variable clinical phenotypes: thus, the dosage of plasma progranulin is a useful tool for a quick and inexpensive large-scale screening of carriers of GRN mutations.
  
  
  OBJECTIVE
  To establish the best cutoff threshold for normal versus abnormal levels of plasma progranulin.
  
  
  METHODS
  309 cognitively healthy controls (25-87 years of age), 72 affected and unaffected GRN+ null mutation carriers (24-86 years of age), 3 affected GRN missense mutation carriers, 342 patients with neurodegenerative diseases and 293 subjects with mild cognitive impairment were enrolled at the Memory Clinic, IRCCS S. Giovanni di Dio-Fatebenefratelli, Brescia, Italy, and at the Alzheimer Unit, Ospedale Maggiore Policlinico and IRCCS Istituto Neurologico C. Besta, Milan, Italy. Plasma progranulin levels were measured using an ELISA kit (AdipoGen Inc., Seoul, Korea).
  
  
  RESULTS
  Plasma progranulin did not correlate with age, gender or body mass index. We established a new plasma progranulin protein cutoff level of 61.55 ng/ml that identifies, with a specificity of 99.6% and a sensitivity of 95.8%, null mutation carriers among subjects attending to a memory clinic. Affected and unaffected GRN null mutation carriers did not differ in terms of circulating progranulin protein (p = 0.686). A significant disease anticipation was observed in GRN+ subjects with the lowest progranulin levels.
  
  
  CONCLUSIONS
  We propose a new plasma progranulin protein cutoff level useful for clinical practice.
authors: Proteomics Unit, IRCCS Centro S. Giovanni di Dio-Fatebenefratelli, Brescia, Italy. rghidoni@fatebenefratelli.it
authors: Roberta
authors: R
authors: Ghidoni
authors: Elena
authors: E
authors: Stoppani
authors: Giacomina
authors: G
authors: Rossi
authors: Elena
authors: E
authors: Piccoli
authors: Valentina
authors: V
authors: Albertini
authors: Anna
authors: A
authors: Paterlini
authors: Michela
authors: M
authors: Glionna
authors: Eleonora
authors: E
authors: Pegoiani
authors: Luigi F
authors: LF
authors: Agnati
authors: Chiara
authors: C
authors: Fenoglio
authors: Elio
authors: E
authors: Scarpini
authors: Daniela
authors: D
authors: Galimberti
authors: Michela
authors: M
authors: Morbin
authors: Fabrizio
authors: F
authors: Tagliavini
authors: Giuliano
authors: G
authors: Binetti
authors: Luisa
authors: L
authors: Benussi
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D060825:Cognitive Dysfunction / Q000097:blood / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics*; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000097:blood* / Q000235:genetics*; D011237:Predictive Value of Tests; D000077153:Progranulins; D012680:Sensitivity and Specificity
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins