Department of Neurology, Emory University School of Medicine, Atlanta, USA.
Department of Biochemistry, Emory University School of Medicine, Atlanta, USA.
Sci Data. 2023 May 9;10(1):261. doi: 10.1038/s41597-023-02158-3.
Alzheimer's disease (AD) is the most common form of dementia, with cerebrospinal fluid (CSF) β-amyloid (Aβ), total Tau, and phosphorylated Tau (pTau) providing the most sensitive and specific biomarkers for diagnosis. However, these diagnostic biomarkers do not reflect the complex changes in AD brain beyond amyloid (A) and Tau (T) pathologies. Here, we report a selected reaction monitoring mass spectrometry (SRM-MS) method with isotopically labeled standards for relative protein quantification in CSF. Biomarker positive (AT+) and negative (AT-) CSF pools were used as quality controls (QCs) to assess assay precision. We detected 62 peptides (51 proteins) with an average coefficient of variation (CV) of ~13% across 30 QCs and 133 controls (cognitively normal, AT-), 127 asymptomatic (cognitively normal, AT+) and 130 symptomatic AD (cognitively impaired, AT+). Proteins that could distinguish AT+ from AT- individuals included SMOC1, GDA, 14-3-3 proteins, and those involved in glycolysis. Proteins that could distinguish cognitive impairment were mainly neuronal proteins (VGF, NPTX2, NPTXR, and SCG2). This demonstrates the utility of SRM-MS to quantify CSF protein biomarkers across stages of AD.
阿尔茨海默病（AD）是最常见的痴呆症形式，脑脊液（CSF）β-淀粉样蛋白（Aβ）、总 Tau 和磷酸化 Tau（pTau）为诊断提供了最敏感和特异的生物标志物。然而，这些诊断生物标志物并不能反映 AD 大脑中除淀粉样（A）和 Tau（T）病理学以外的复杂变化。在这里，我们报告了一种使用同位素标记标准品的选择反应监测质谱（SRM-MS）方法，用于相对 CSF 中蛋白质的定量。生物标志物阳性（AT+）和阴性（AT-）CSF 池用作质量控制（QC），以评估分析的精密度。我们在 30 个 QC 和 133 个对照（认知正常，AT-）、127 个无症状（认知正常，AT+）和 130 个有症状 AD（认知障碍，AT+）中检测到 62 个肽（51 种蛋白质），平均变异系数（CV）约为 13%。能够区分 AT+和 AT-个体的蛋白质包括 SMOC1、GDA、14-3-3 蛋白和参与糖酵解的蛋白质。能够区分认知障碍的蛋白质主要是神经元蛋白（VGF、NPTX2、NPTXR 和 SCG2）。这证明了 SRM-MS 在 AD 各阶段定量 CSF 蛋白质生物标志物的实用性。
