Title: Serum biomarker for progranulin-associated frontotemporal lobar degeneration
Authors: Sleegers, Kristel ×
Brouwers, Nathalie
Van Damme, Philip
Engelborghs, Sebastiaan
Gijselinck, Ilse
van der Zee, Julie
Peeters, Karin
Mattheijssens, Maria
Cruts, Marc
Vandenberghe, Rik
De Deyn, Peter P
Robberecht, Wim
Van Broeckhoven, Christine #
Issue Date: May-2009
Publisher: American Neurological Association
Series Title: Annals of Neurology vol:65 issue:5 pages:603-609
Abstract: OBJECTIVE: Mutations that lead to a loss of progranulin (PGRN) explain a considerable portion of the occurrence of frontotemporal lobar degeneration. We tested a biomarker allowing rapid detection of a loss of PGRN. METHODS: We used an enzyme-linked immunosorbent assay to measure in serum the PGRN protein levels of six affected and eight unaffected carriers from within an extended Belgian founder family segregating the null mutation IVS1+5G>C. Further, we measured serum PGRN levels in 2 patients with another null mutation (a Met1 and a frameshift mutation), in 4 patients carrying a predicted pathogenic missense mutation and in 5 patients carrying a benign missense polymorphism, in 9 unaffected noncarrier relatives, and in 22 community controls. RESULTS: Serum PGRN levels were reduced in both affected and unaffected null mutation carriers compared with noncarrier relatives (p(exact) < 0.0001), and allowed perfect discrimination between carriers and noncarriers (sensitivity: 1.0; 1 - specificity: 0.0). Serum PGRN levels in Cys139Arg and Arg564Cys mutation carriers were significantly lower than in controls, but greater than in null mutation carriers, fitting the hypothesis of partial loss of function caused by these missense mutations. As expected, levels for carriers of benign missense polymorphisms were not significantly different from controls. INTERPRETATION: Our results indicate that the serum PGRN level is a reliable biomarker for diagnosing and early detection of frontotemporal lobar degeneration caused by PGRN null mutations, and provided the first in vivo evidence that at least some missense mutations in PGRN may lead to a (partial) loss of PGRN.
ISSN: 0364-5134
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Neurology
Laboratory for Cognitive Neurology
Laboratory for Neurobiology (Vesalius Research Center)
× corresponding author
# (joint) last author

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