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Am J Neurodegener Dis 2012;1(2):180-190

Review Article
Circulating progranulin as a biomarker for neurodegenerative diseases

Roberta Ghidoni, Anna Paterlini, Luisa Benussi

Proteomics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; NeuroBioGen Lab-Memory
Clinic, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

Received July 20, 2012; accepted August 1, 2012; Epub August 2, 2012; published August 15, 2012

Abstract: Progranulin is a growth factor involved in the regulation of multiple processes including tumorigenesis,
wound repair, development, and inflammation. The recent discovery that mutations in the gene encoding for
progranulin (GRN) cause frontotemporal lobar degeneration (FTLD), and other neurodegenerative diseases leading to
dementia, has brought renewed interest in progranulin and its functions in the central nervous system. GRN null
mutations cause protein haploinsufficiency, leading to a significant decrease in progranulin levels that can be detected
in plasma, serum and cerebrospinal fluid (CSF) of mutation carriers. The dosage of circulating progranulin sped up
the identification of GRN mutations thus favoring genotype-phenotype correlation studies. Researchers demonstrated
that, in GRN null mutation carriers, the shortage of progranulin invariably precedes clinical symptoms and thus
mutation carriers are “captured” regardless of their disease status. GRN is a particularly appealing gene for drug
targeting, in the way that boosting its expression may be beneficial for mutation carriers, preventing or delaying the
onset of GRN-related neurodegenerative diseases. Physiological regulation of progranulin expression level is only
partially known. Progranulin expression reflects mutation status and, intriguingly, its levels can be modulated by some
additional factor (i.e. genetic background; drugs). Thus, factors increasing the production and secretion of progranulin
from the normal gene are promising potential therapeutic avenues. In conclusion, peripheral progranulin is a
nonintrusive highly accurate biomarker for early identification of mutation carriers and for monitoring future treatments
that might boost the level of this protein. (AJND1207004).

Keywords: Progranulin, haploinsufficiency, cut-off, blood, CSF, expression, frontotemporal, dementia, GRN, modulator

Address all correspondence to:
Dr. Roberta Ghidoni
Proteomics Unit
IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia
via Pilastroni 4, 25125 Brescia, Italy.
Tel. +39 030 3501725; Fax. +39 030 3533513
E-mail: rghidoni@fatebenefratelli.it