Department of Neurology, Taipei Medical University Hospital, Taipei 110, Taiwan; Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
Clin Biochem. 2020 Feb;76:24-30. doi: 10.1016/j.clinbiochem.2019.11.011. Epub 2019 Nov 28.
The development of blood-based biomarkers for early diagnosis and treatment of Alzheimer's disease (AD) is desirable. In AD model mouse brain and neuronal cells, Abelson helper integration site-1 (AHI1) protein is reduced. AHI1 facilitates intracellular amyloid precursor protein (APP) translocation to inhibit amyloidogenic pathology of AD, and thus may be an AD biomarker.
This study was conducted among 32 AD patients and 54 healthy control (HC) subjects. AHI1-related protein levels from initially collected serum samples in each group were screened using Western blotting. The protein concentrations of AHI1 and amyloid-β (Aβ), peptide(s) derived from APP, from all serum samples were analyzed using ELISA.
In AD serum, AHI1 and a large truncated C-terminal APP fragment were significantly reduced. The average concentrations of serum AHI1 and Aβ in AD were significantly lower than those in HC. Notably, AHI1 concentration in HC serum was decreased in an age-dependent manner, while it was consistently low in AD serum and had no correlation with Aβ or mini-mental state examination score. The receiver operating characteristic analysis on all subjects demonstrated an area under curve (AUC) value of 0.7 for AHI1 on AD diagnosis, while the AUC increased to 0.82 on the subjects younger than 77 years old, suggesting a good diagnostic performance of serum AHI1 for AD especially at relatively young age.
An early event of AHI1 reduction in the body of AD patients was observed. Serum AHI1 may be valuable for early diagnosis of AD.
开发用于阿尔茨海默病（AD）早期诊断和治疗的基于血液的生物标志物是可取的。在 AD 模型小鼠大脑和神经元细胞中，Abelson 辅助整合位点-1（AHI1）蛋白减少。AHI1 促进细胞内淀粉样前体蛋白（APP）易位，以抑制 AD 的淀粉样病理，因此可能是 AD 的生物标志物。
本研究在 32 名 AD 患者和 54 名健康对照（HC）受试者中进行。使用 Western blot 筛选每组最初收集的血清样本中的 AHI1 相关蛋白水平。使用 ELISA 分析所有血清样本中 AHI1 和淀粉样β（Aβ）、APP 衍生肽（s）的蛋白浓度。
在 AD 血清中，AHI1 和大的截断 C 端 APP 片段显著减少。AD 血清中 AHI1 和 Aβ 的平均浓度明显低于 HC。值得注意的是，HC 血清中 AHI1 浓度随年龄呈下降趋势，而 AD 血清中 AHI1 浓度持续较低，与 Aβ或简易精神状态检查评分无关。对所有受试者的受试者工作特征分析显示，AHI1 对 AD 诊断的曲线下面积（AUC）值为 0.7，而年龄小于 77 岁的受试者的 AUC 增加到 0.82，表明血清 AHI1 对 AD 的诊断性能良好，尤其是在相对年轻的年龄。
在 AD 患者的体内观察到 AHI1 减少的早期事件。血清 AHI1 可能对 AD 的早期诊断有价值。
