Dulewicz Maciej, Kulczyńska-Przybik Agnieszka, Słowik Agnieszka, Borawska Renata, Mroczko Barbara
Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland.
Department of Neurology, Jagiellonian University, 30-688 Krakow, Poland.
J Clin Med. 2021 Oct 2;10(19):4575. doi: 10.3390/jcm10194575.
Synaptic loss and dysfunction are one of the earliest signs of neurodegeneration associated with cognitive decline in Alzheimer's disease (AD). It seems that by assessing proteins related to synapses, one may reflect their dysfunction and improve the understanding of neurobiological processes in the early stage of the disease. To our best knowledge, this is the first study that analyzes the CSF concentrations of two synaptic proteins together, such as neurogranin (Ng) and neuronal pentraxins receptor (NPTXR) in relation to neurochemical dementia biomarkers in Alzheimer's disease.
Ng, NPTXR and classical AD biomarkers concentrations were measured in the CSF of patients with AD and non-demented controls (CTRL) using an enzyme-linked immunosorbent assay (ELISA) and Luminex xMAP technology.
The CSF level of Ng was significantly higher, whereas the NPTXR was significantly lower in the AD patients than in cognitively healthy controls. As a first, we calculated the NPTXR/Ng ratio as an indicator of synaptic disturbance. The patients with AD presented a significantly decreased NPTXR/Ng ratio. The correlation was observed between both proteins in the AD and the whole study group. Furthermore, the relationship between the Ng level and pTau181 was found in the AD group of patients.
The Ng and NPTXR concentrations in CSF are promising synaptic dysfunction biomarkers reflecting pathological changes in AD.
突触丧失和功能障碍是与阿尔茨海默病(AD)认知衰退相关的神经退行性变的最早迹象之一。似乎通过评估与突触相关的蛋白质,可以反映其功能障碍并增进对该疾病早期神经生物学过程的理解。据我们所知,这是第一项同时分析两种突触蛋白(如神经颗粒蛋白(Ng)和神经元五聚体受体(NPTXR))的脑脊液浓度与阿尔茨海默病神经化学痴呆生物标志物之间关系的研究。
使用酶联免疫吸附测定(ELISA)和Luminex xMAP技术测量AD患者和非痴呆对照(CTRL)脑脊液中Ng、NPTXR和经典AD生物标志物的浓度。
与认知健康对照相比,AD患者脑脊液中Ng水平显著升高,而NPTXR水平显著降低。首先,我们计算了NPTXR/Ng比值作为突触紊乱的指标。AD患者的NPTXR/Ng比值显著降低。在AD组和整个研究组中均观察到这两种蛋白质之间的相关性。此外,在AD患者组中发现Ng水平与pTau181之间存在关联。
脑脊液中Ng和NPTXR浓度有望成为反映AD病理变化的突触功能障碍生物标志物。