Optimal plasma progranulin cutoff value for predicting null progranulin mutations in neurodegenerative diseases: a multicenter Italian study.
Neurodegener Dis
; 9(3): 121-7, 2012.
Article
em En
| MEDLINE
| ID: mdl-22123177
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Neurodegenerativas
/
Peptídeos e Proteínas de Sinalização Intercelular
/
Mutação
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Neurodegener Dis
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Itália