TY - JOUR
T1 - Optimal plasma progranulin cutoff value for predicting null progranulin mutations in neurodegenerative diseases
T2 - A multicenter Italian study
AU - Ghidoni, Roberta
AU - Stoppani, Elena
AU - Rossi, Giacomina
AU - Piccoli, Elena
AU - Albertini, Valentina
AU - Paterlini, Anna
AU - Glionna, Michela
AU - Pegoiani, Eleonora
AU - Agnati, Luigi F.
AU - Fenoglio, Chiara
AU - Scarpini, Elio
AU - Galimberti, Daniela
AU - Morbin, Michela
AU - Tagliavini, Fabrizio
AU - Binetti, Giuliano
AU - Benussi, Luisa
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
KW - Biomarker
KW - Frontotemporal lobar degeneration
KW - GRN
KW - Neurodegeneration
KW - Plasma cutoff
KW - Translational research
UR - http://www.scopus.com/inward/record.url?scp=84858997674&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858997674&partnerID=8YFLogxK
U2 - 10.1159/000333132
DO - 10.1159/000333132
M3 - Article
C2 - 22123177
AN - SCOPUS:84858997674
VL - 9
SP - 121
EP - 127
JO - Neurodegenerative Diseases
JF - Neurodegenerative Diseases
SN - 1660-2854
IS - 3
ER -