Progranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation Carriers.
Progranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation Carriers.
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DOI：
10.1159/000447738
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发表时间：
2016-05
影响因子：
2.3
通讯作者：
van Swieten JC
中科院分区：
文献类型：
--
作者：
Meeter LH;Patzke H;Loewen G;Dopper EG;Pijnenburg YA;van Minkelen R;van Swieten JC
颗粒蛋白基因（GRN）的致病性突变在5-10%的额颞叶痴呆（FTD）患者中是致病的，主要导致颗粒蛋白前蛋白（PGRN）水平降低。即将进行的治疗试验的重点是提高PGRN水平。研究了血浆PGRN （n = 41）的波动及其与脑脊液（CSF, n = 32）和特异性单核苷酸多态性的关系。携带者血浆PGRN水平低于对照组，1周内携带者的平均变异系数为5.3%。尽管携带者血浆PGRN与脑脊液PGRN相关（r = 0.54, p = 0.02），但血浆仅解释了脑脊液PGRN变异的29%。rss5848、rs646776和rs1990622基因型只能部分解释受试者之间PGRN水平的差异。血浆PGRN在1周内相对稳定，因此似乎适合用于PGRN增强剂的治疗监测。由于血浆PGRN与脑脊液PGRN仅中度相关，因此在治疗试验中还需要脑脊液取样。
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. 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. 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. 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.