Progranulin protein levels are differently regulated in plasma and CSF
Progranulin protein levels are differently regulated in plasma and CSF
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DOI：
10.1212/wnl.0000000000000445
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发表时间：
2014-05-27
期刊：
影响因子：
9.9
通讯作者：
Rademakers, Rosa
中科院分区：
文献类型：
--
作者：
Nicholson, Alexandra M.;Finch, NiCole A.;Rademakers, Rosa
目的：我们的目的是探讨血浆和脑脊液颗粒蛋白前体（PGRN）水平之间的关系：血浆和脑脊液PGRN测定在一个队列的345例受试者从马约诊所研究老化ELISA。单核苷酸多态性基因分型采用TaqMan分析。使用单变量线性回归模型分别研究了脑脊液和血浆中PGRN与性别、样本采集时年龄、诊断、单核苷酸多态性基因型（GRN、SORT 1和APOE）和匹兹堡复合物B评分之间的关系。结果：血浆PGRN（p = 0.0031）和脑脊液PGRN（p = 0.0044）随年龄增长而显著增加，男性血浆PGRN水平比女性低7%（p = 0.0025），脑脊液PGRN水平比女性高5%（p = 0.0024）。校正年龄和性别后，较高的血浆PGRN与较高的CSF PGRN相关（部分r = 0.17，p = 0.004）。在血浆中，rs 5848（GRN; p = 0.002）和rs646776（SORT 1; p = 3.56 E-7）均与PGRN相关，而在CSF中仅rs 5848显示出高度显著的相关性（p = 5.59 E-14）。年龄、性别、rs 5848基因型和血浆PGRN一起仅占CSF PGRN中观察到的变异性的18%。结论：虽然血浆和CSF PGRN之间存在一定的相关性，但年龄、性别和遗传因素不同地影响PGRN水平。因此，在使用血浆PGRN预测脑中PGRN变化时应谨慎。这些发现进一步强调了血浆PGRN水平可能无法准确预测临床特征或对未来额颞叶变性治疗的反应。
Objective: We aimed to investigate the relationship between plasma and CSF progranulin (PGRN) levels.Methods: Plasma and CSF PGRN were measured in a cohort of 345 subjects from the Mayo Clinic Study of Aging by ELISA. Single nucleotide polymorphism genotyping was performed using TaqMan assays. Associations between PGRN and sex, age at sample collection, diagnosis, single nucleotide polymorphism genotypes (GRN, SORT1, and APOE), and Pittsburgh compound B score were explored separately in CSF and plasma using single variable linear regression models. Pearson partial correlation coefficient was used to estimate the correlation of PGRN in CSF and plasma.Results: Plasma (p = 0.0031) and CSF (p = 0.0044) PGRN significantly increased with age, whereas plasma PGRN levels were 7% lower (p = 0.0025) and CSF PGRN levels 5% higher (p = 0.0024) in male compared with female participants. Correcting for age and sex, higher plasma PGRN was associated with higher CSF PGRN (partial r = 0.17, p = 0.004). In plasma, both rs5848 (GRN; p = 0.002) and rs646776 (SORT1; p = 3.56E-7) were associated with PGRN, while only rs5848 showed highly significant association in CSF (p = 5.59E-14). Age, sex, rs5848 genotype, and plasma PGRN together accounted for only 18% of the variability observed in CSF PGRN.Conclusions: While some correlation exists between plasma and CSF PGRN, age, sex, and genetic factors differently affect PGRN levels. Therefore, caution should be taken when using plasma PGRN to predict PGRN changes in the brain. These findings further highlight that plasma PGRN levels may not accurately predict clinical features or response to future frontotemporal lobar degeneration therapies.