Departamento de Bioquímica y Biología Molecular, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Departamento de Ciencias de la Salud, Facultad de Ciencias Biomédicas y de la Salud, Universidad Europea de Madrid, 28670 Madrid, Spain.
Int J Mol Sci. 2023 Jun 30;24(13):10897. doi: 10.3390/ijms241310897.
Over the last few years, intense research efforts have been made to anticipate or improve the diagnosis of Alzheimer's disease by detecting blood biomarkers. However, the most promising blood biomarkers identified to date have some limitations, most of them related to the techniques required for their detection. Hence, new blood biomarkers should be identified to improve the diagnosis of AD, better discriminate between AD and mild cognitive impairment (MCI) and identify cognitively unimpaired (CU) older individuals at risk for progression to AD. Our previous studies demonstrated that both the purinergic receptor P2X7 and the tissue-nonspecific alkaline phosphatase ectoenzyme (TNAP) are upregulated in the brains of AD patients. Since both proteins are also present in plasma, we investigated whether plasma P2X7R and TNAP are altered in MCI and AD patients and, if so, their potential role as AD biomarkers. We found that AD but not MCI patients present increased plasma P2X7R levels. Nevertheless, TNAP plasma activity was increased in MCI patients and decreased in the AD group. ROC curve analysis indicated that measuring both parameters has a reasonable discriminating capability to diagnose MCI and AD conditions. In addition to confirming that individuals progressing to MCI have increased TNAP activity in plasma, longitudinal studies also revealed that CU individuals have lower plasma TNAP activity than stable controls. Thus, we propose that P2X7 and TNAP could serve as new plasma biomarkers for MCI and AD.
在过去的几年中，人们进行了大量的研究工作，试图通过检测血液生物标志物来预测或改善阿尔茨海默病的诊断。然而，迄今为止发现的最有前途的血液生物标志物存在一些局限性，其中大多数与检测所需的技术有关。因此，应该识别新的血液生物标志物，以改善 AD 的诊断，更好地区分 AD 和轻度认知障碍（MCI），并识别认知未受损（CU）的老年人进展为 AD 的风险。我们之前的研究表明，嘌呤能受体 P2X7 和组织非特异性碱性磷酸酶外切酶（TNAP）在 AD 患者的大脑中均上调。由于这两种蛋白也存在于血浆中，我们研究了血浆 P2X7R 和 TNAP 在 MCI 和 AD 患者中是否发生改变，如果发生改变，它们是否有可能成为 AD 的生物标志物。我们发现 AD 患者而非 MCI 患者的血浆 P2X7R 水平升高。然而，MCI 患者的 TNAP 血浆活性增加，而 AD 组则减少。ROC 曲线分析表明，测量这两个参数具有合理的鉴别能力，可以诊断 MCI 和 AD 状态。除了证实进展为 MCI 的个体的血浆 TNAP 活性增加外，纵向研究还表明，CU 个体的血浆 TNAP 活性低于稳定对照者。因此，我们提出 P2X7 和 TNAP 可以作为 MCI 和 AD 的新型血浆生物标志物。
