HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: 01.wnl.0000325058.10218.fcv1 71/16/1235    most recent Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ghidoni, R. Articles by Binetti, G. Search for Related Content PubMed PubMed Citation Articles by Ghidoni, R. Articles by Binetti, G. Related Collections Frontotemporal dementia Corticobasal degeneration Cerebrospinal Fluid All Genetics

Low plasma progranulin levels predict progranulin mutations in frontotemporal lobar degeneration

From the NeuroBioGen Lab-Memory Clinic, IRCCS "Centro S. Giovanni di Dio-FBF," Brescia, Italy.

Address correspondence and reprint requests to Dr. Giuliano Binetti, NeuroBioGen Lab-Memory Clinic, IRCCS "Centro San Giovanni di Dio-Fatebenefratelli," via Pilastroni 4, 25125 Brescia, Italy

Background: Mutations in the progranulin gene (PGRN) were identified as the causal mechanism underlying frontotemporal lobar degeneration (FTLD). Most of these mutations are predicted to create null alleles leading to a 50% loss of progranulin transcript.

Methods: Patients underwent clinical and neurologic examination at the Memory Clinic of the IRCCS S. Giovanni di Dio-Fatebenefratelli, Brescia, Italy. We enrolled affected (n = 6) and unaffected at risk members (n = 73) of families carrying the FTLD associated progranulin Leu271LeufsX10 mutation; additionally, we included subjects affected by sporadic/familial FTLD (n = 65), controls (n = 75), and a family carrying the tau P301L mutation. The presence of mutations in PGRN and MAPT genes was investigated by direct sequencing of exonic and flanking intronic regions. Progranulin plasma and CSF levels were measured using ELISA.

Results: We demonstrated that progranulin protein is strongly reduced (up to 3.93-fold) both in plasma and CSF of affected and unaffected subjects carrying mutations in progranulin gene (PGRN Leu271LeufsX10 and Q341X). We established a plasma progranulin protein cutoff level of 74.4 ng/mL that identifies, with specificity and sensitivity of 100%, mutation carriers among unaffected subjects. In FTLD, values 110.9 ng/mL give a specificity of 92.8% and a sensitivity of 100% for PGRN mutations.

Conclusions: We propose the dosage of plasma progranulin as a useful tool for a quick and inexpensive large-scale screening of carriers of progranulin mutations and for monitoring future treatments that might boost the level of this protein.

GLOSSARY: FTD = frontotemporal dementia; FTLD = frontotemporal lobar degeneration; PPA = primary nonfluent aphasia.

e-Pub ahead of print on September 3, 2008, at www.neurology.org.

Supported by grants RC2007, 2005/agreement number PS-NEURO ex56/05/4, and 2004/agreement number 533/F/B 1, Italian Ministry of Health.

Disclosure: The authors report no disclosures.

neurobiologia{at}fatebenefratelli.it

Received February 25, 2008. Accepted in final form May 27, 2008.

This article has been cited by other articles:

				N. Finch, M. Baker, R. Crook, K. Swanson, K. Kuntz, R. Surtees, G. Bisceglio, A. Rovelet-Lecrux, B. Boeve, R. C. Petersen, et al. Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members Brain, March 1, 2009; 132(3): 583 - 591. [Abstract] [Full Text] [PDF]

				T. D. Bird Progranulin plasma levels in the diagnosis of frontotemporal dementia Brain, March 1, 2009; 132(3): 568 - 569. [Full Text] [PDF]