Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
Brain Res. 2010 Nov 29;1362:13-22. doi: 10.1016/j.brainres.2010.09.073. Epub 2010 Sep 25.
Synaptic pathology occurs early in Alzheimer's disease (AD) development, and cerebrospinal fluid biomarkers for synaptic damage may be altered early in the disease process. In the present study we examined cerebrospinal fluid levels of the postsynaptic protein neurogranin in patients with mild cognitive impairment (MCI) or AD and controls. The low neurogranin level in cerebrospinal fluid required enrichment by immunoprecipitation prior to mass spectrometric identification and semi-quantitative immunoblot analysis. Relative quantification revealed a significant increase of neurogranin in the AD group compared with controls, while the MCI group was not statistically different from either controls or the AD group. The concentrations of the AD biomarkers T-tau, P-tau(181) and Aβ(42) were significantly changed in the control and MCI groups compared with the AD group, but no significant differences were found between the MCI group and controls for the three biomarkers. Nevertheless, a trend towards increasing levels of neurogranin, T-tau and P-tau(181) was found in cerebrospinal fluid from MCI patients compared with controls. The elevated neurogranin levels in the MCI and AD groups might reflect synaptic degeneration. These results together suggest that cerebrospinal fluid neurogranin might be valuable together with the established AD biomarkers in the early diagnosis of AD and warrants further studies to determine the diagnostic value of neurogranin.
突触病理学发生在阿尔茨海默病（AD）发展的早期，脑脊液中突触损伤的生物标志物可能在疾病早期发生改变。在本研究中，我们检测了轻度认知障碍（MCI）或 AD 患者及对照组脑脊液中突触后蛋白神经颗粒蛋白的水平。由于脑脊液中神经颗粒蛋白的水平较低，在进行质谱鉴定和半定量免疫印迹分析之前，需要通过免疫沉淀进行富集。相对定量分析显示，AD 组脑脊液中的神经颗粒蛋白水平显著升高，而 MCI 组与对照组或 AD 组均无统计学差异。与 AD 组相比，对照组和 MCI 组的 AD 生物标志物 T-tau、P-tau(181)和 Aβ(42)的浓度明显改变，但 MCI 组与对照组在这三个标志物上没有发现显著差异。然而，与对照组相比，MCI 患者脑脊液中的神经颗粒蛋白、T-tau 和 P-tau(181)水平呈升高趋势。MCI 和 AD 组中升高的神经颗粒蛋白水平可能反映了突触退化。这些结果表明，脑脊液神经颗粒蛋白可能与已建立的 AD 生物标志物一起，有助于 AD 的早期诊断，值得进一步研究以确定神经颗粒蛋白的诊断价值。
