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.
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.
Authors: A Alberici; S Archetti; A Pilotto; E Premi; M Cosseddu; A Bianchetti; F Semeraro; M Salvetti; M L Muiesan; A Padovani; B Borroni Journal: Neurol Sci Date: 2014-02-26 Impact factor: 3.307
Authors: Leonel T Takada; Valeria S Bahia; Henrique C Guimarães; Thais V M M Costa; Thiago C Vale; Roberta D Rodriguez; Fabio H G Porto; João C B Machado; Rogério G Beato; Karolina G Cesar; Jerusa Smid; Camila F Nascimento; Lea T Grinberg; Sonia M D Brucki; Jessica R Maximino; Sarah T Camargos; Gerson Chadi; Paulo Caramelli; Ricardo Nitrini Journal: Alzheimer Dis Assoc Disord Date: 2016 Oct-Dec Impact factor: 2.703
Authors: Katherine R Smith; John Damiano; Silvana Franceschetti; Stirling Carpenter; Laura Canafoglia; Michela Morbin; Giacomina Rossi; Davide Pareyson; Sara E Mole; John F Staropoli; Katherine B Sims; Jada Lewis; Wen-Lang Lin; Dennis W Dickson; Hans-Henrik Dahl; Melanie Bahlo; Samuel F Berkovic Journal: Am J Hum Genet Date: 2012-05-17 Impact factor: 11.025
Authors: Alexandra M Nicholson; Nicole A Finch; Aleksandra Wojtas; Matt C Baker; Ralph B Perkerson; Monica Castanedes-Casey; Linda Rousseau; Luisa Benussi; Giuliano Binetti; Roberta Ghidoni; Ging-Yuek R Hsiung; Ian R Mackenzie; Elizabeth Finger; Bradley F Boeve; Nilüfer Ertekin-Taner; Neill R Graff-Radford; Dennis W Dickson; Rosa Rademakers Journal: J Neurochem Date: 2013-07-01 Impact factor: 5.372