期刊
DEMENTIA AND GERIATRIC COGNITIVE DISORDERS EXTRA
卷 6, 期 2, 页码 330-340出版社
KARGER
DOI: 10.1159/000447738
关键词
Frontotemporal dementia; Progranulin protein; Granulin gene (GRN); Plasma; Cerebrospinal fluid; Biomarker; Single nucleotide polymorphism
资金
- FORUM Pharmaceuticals Inc.
- 'Nationaal Initiatief Hersenen en Cognitie', Alzheimer Nederland [056-13-018]
- Van Leersumfonds [VLF2013220]
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. (C) 2016 The Author(s) Published by S. Karger AG, Basel
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