Background

Parathyroid hormone-related protein (PTHrP) is involved in intracellular calcium regulation, neural cell proliferation and synaptic transmission. To date, no studies have been performed to evaluate the potential of PTHrP concentrations in cerebrospinal fluid (CSF) as a biomarker of brain pathophysiology. In this study we evaluated the association between CSF concentrations of PTHrP with the core CSF biomarkers of Alzheimer’s disease (AD).

Methods

PTHrP and calcium were analysed using validated mass spectrometry based methods in a set of CSF samples that tested positive (n = 45) and negative (n = 45) for the AD biomarkers, including total tau protein (T-tau), phosphorylated tau protein (P-tau) and amyloid-β 42 (Aβ42). The measured CSF concentrations of PTHrP and calcium (Ca) were evaluated for association with AD CSF biomarkers.

Results

PTHrP and Ca concentrations in CSF samples ranged between 25 and 137 pmol/L and 0.92–1.53 mmol/L, respectively. Higher concentrations of PTHrP were observed in association with increased concentrations of T-tau and P-tau in the AD and the control group; while a stronger correlation was observed in the control group (ρ = 0.6, p < 0.0001; and ρ = 0.72, p < 0.0001, for T-tau and P-tau, respectively). Negative correlation was observed between concentrations of PTHrP and Aβ42 in the AD group (ρ = 0.27, p = 0.015). A statistically significantly lower ratio Aβ42/PTHrP was observed in the AD group (p < 0.0001).

Conclusion

In the current study, we observed an association of PTHrP concentrations with concentrations of clinically used CSF biomarkers of AD. Concentrations of PTHrP were positively correlated with concentrations of T-tau and P-tau, suggesting an association with neuronal secretion and function, which is reduced upon progression to AD pathology. Our data suggest potential utility of the Aβ42/PTHrP ratio in assessment of AD progression.

中文翻译：

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脑脊液中 PTHrP 水平与阿尔茨海默病生物标志物的关联

背景

甲状旁腺激素相关蛋白 (PTHrP) 参与细胞内钙调节、神经细胞增殖和突触传递。迄今为止，尚未进行研究来评估脑脊液 (CSF) 中 PTHrP 浓度作为脑病理生理学生物标志物的潜力。在这项研究中，我们评估了脑脊液 PTHrP 浓度与阿尔茨海默病 (AD) 的核心脑脊液生物标志物之间的关联。

方法

在一组 CSF 样本中使用经过验证的基于质谱的方法分析 PTHrP 和钙，这些样本测试了 AD 生物标志物的阳性 (n = 45) 和阴性 (n = 45)，包括总 tau 蛋白 (T-tau)、磷酸化 tau 蛋白(P-tau) 和淀粉样蛋白-β 42 (Aβ42)。评估测量的 PTHrP 和钙 (Ca) 的 CSF 浓度与 AD CSF 生物标志物的关联。

结果

脑脊液样本中的 PTHrP 和 Ca 浓度分别在 25 和 137 pmol/L 和 0.92-1.53​​ mmol/L 之间。观察到较高浓度的 PTHrP 与 AD 和对照组中 T-tau 和 P-tau 浓度的增加有关；而在对照组中观察到更强的相关性（对于 T-tau 和 P-tau，分别为 ρ = 0.6，p < 0.0001；和 ρ = 0.72，p < 0.0001）。AD 组中 PTHrP 和 Aβ42 的浓度呈负相关（ρ = 0.27，p = 0.015）。在 AD 组中观察到 Aβ42/PTHrP 的比率在统计学上显着降低（p < 0.0001）。

结论

在目前的研究中，我们观察到 PTHrP 浓度与临床使用的 AD 脑脊液生物标志物浓度之间存在关联。PTHrP 的浓度与 T-tau 和 P-tau 的浓度呈正相关，表明与神经元分泌和功能相关，在进展为 AD 病理时会降低。我们的数据表明 Aβ42/PTHrP 比率在评估 AD 进展中的潜在效用。