Optimal plasma progranulin cutoff value for predicting null progranulin mutations in neurodegenerative diseases: A multicenter Italian study

Roberta Ghidoni, Elena Stoppani, Giacomina Rossi, Elena Piccoli, Valentina Albertini, Anna Paterlini, Michela Glionna, Eleonora Pegoiani, Luigi F. Agnati, Chiara Fenoglio, Elio Scarpini, Daniela Galimberti, Michela Morbin, Fabrizio Tagliavini, Giuliano Binetti, Luisa Benussi

Research output: Contribution to journalArticle

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. Conclusion: We propose a new plasma progranulin protein cutoff level useful for clinical practice.

Original languageEnglish
Pages (from-to)121-127
Number of pages7
JournalNeurodegenerative Diseases
Volume9
Issue number3
DOIs
Publication statusPublished - Mar 2012

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Keywords

  • Biomarker
  • Frontotemporal lobar degeneration
  • GRN
  • Neurodegeneration
  • Plasma cutoff
  • Translational research

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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