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Updated: Mar 14, 2026
Modified Yeast-Two-Hybrid System to Identify Proteins Interacting with the Growth Factor Progranulin
Published on: January 17, 2012
Progranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation Carriers
Lieke H H Meeter1, Holger Patzke2, Gordon Loewen2
1Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
Background:
Pathogenic mutations in the granulin gene (GRN) are causative in 5-10% of patients with frontotemporal dementia (FTD), mostly leading to reduced progranulin protein (PGRN) levels. Upcoming therapeutic trials focus on enhancing PGRN levels.
Methods:
Fluctuations in plasma PGRN (n = 41) and its relationship with cerebrospinal fluid (CSF, n = 32) and specific single nucleotide polymorphisms were investigated in pre- and symptomatic GRN mutation carriers and controls.
Results:
Plasma PGRN levels were lower in carriers than in controls and showed a mean coefficient of variation of 5.3% in carriers over 1 week. Although plasma PGRN correlated with CSF PGRN in carriers (r = 0.54, p = 0.02), plasma only explained 29% of the variability in CSF PGRN. rs5848, rs646776 and rs1990622 genotypes only partly explained the variability of PGRN levels between subjects.
Conclusions:
Plasma PGRN is relatively stable over 1 week and therefore seems suitable for treatment monitoring of PGRN-enhancing agents. Since plasma PGRN only moderately correlated with CSF PGRN, CSF sampling will additionally be needed in therapeutic trials.
