Division of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China.
Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
Alzheimers Dement. 2022 Jan;18(1):88-102. doi: 10.1002/alz.12369. Epub 2021 May 25.
Blood proteins are emerging as candidate biomarkers for Alzheimer's disease (AD). We systematically profiled the plasma proteome to identify novel AD blood biomarkers and develop a high-performance, blood-based test for AD.
We quantified 1160 plasma proteins in a Hong Kong Chinese cohort by high-throughput proximity extension assay and validated the results in an independent cohort. In subgroup analyses, plasma biomarkers for amyloid, tau, phosphorylated tau, and neurodegeneration were used as endophenotypes of AD.
We identified 429 proteins that were dysregulated in AD plasma. We selected 19 "hub proteins" representative of the AD plasma protein profile, which formed the basis of a scoring system that accurately classified clinical AD (area under the curve = 0.9690-0.9816) and associated endophenotypes. Moreover, specific hub proteins exhibit disease stage-dependent dysregulation, which can delineate AD stages.
This study comprehensively profiled the AD plasma proteome and serves as a foundation for a high-performance, blood-based test for clinical AD screening and staging.
血液蛋白正逐渐成为阿尔茨海默病（AD）的候选生物标志物。我们系统地分析了血浆蛋白质组，以鉴定新的 AD 血液生物标志物，并开发一种用于 AD 的高性能血液检测方法。
我们通过高通量邻近延伸分析对香港华人队列中的 1160 种血浆蛋白进行定量，并在独立队列中验证了结果。在亚组分析中，淀粉样蛋白、tau、磷酸化 tau 和神经退行性变的血浆生物标志物被用作 AD 的内表型。
我们确定了 429 种在 AD 血浆中失调的蛋白质。我们选择了 19 种“枢纽蛋白”作为 AD 血浆蛋白谱的代表，这些蛋白构成了评分系统的基础，该系统能够准确地对临床 AD（曲线下面积 = 0.9690-0.9816）和相关内表型进行分类。此外，特定的枢纽蛋白表现出与疾病阶段相关的失调，这可以描绘 AD 阶段。
本研究全面分析了 AD 血浆蛋白质组，为临床 AD 筛查和分期的高性能血液检测方法奠定了基础。
