Mattsson Niklas, Lönneborg Anders, Boccardi Marina, Blennow Kaj, Hansson Oskar
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden; Department of Neurology, Skåne University Hospital, Lund, Sweden.
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Neurobiol Aging. 2017 Apr;52:196-213. doi: 10.1016/j.neurobiolaging.2016.02.034.
Novel diagnostic criteria for Alzheimer's disease (AD) incorporate biomarkers, but their maturity for implementation in clinical practice at the prodromal stage (mild cognitive impairment [MCI]) is unclear. Here, we evaluate cerebrospinal fluid (CSF) β-amyloid (Aβ42), total tau, and phosphorylated tau in the light of a 5-phase framework for biomarker development. Ample evidence is available for phase 1 (identifying useful leads) and phase 2 (assessing the accuracy for AD dementia versus controls) for CSF biomarkers. Phase 3 (utility in MCI) is partially achieved. In cohorts with long follow-up time, CSF Aβ42, total tau, and phosphorylated tau have high diagnostic accuracy for MCI due to AD. Phase 4 (performance in real world) is ongoing, and phase 5 studies (quantify impact and costs) are to come. Our results highlight priorities to pursue and to enable the proper use of CSF biomarkers in the clinic. Priorities are to reduce measurement variability by introduction of fully automated assay systems; to increase diagnostic specificity toward non-AD neurocognitive diseases at the MCI stage; and to clarify the role of CSF biomarkers versus other biomarker modalities in clinical practice and in design of clinical trials. These efforts are currently ongoing.
阿尔茨海默病（AD）的新型诊断标准纳入了生物标志物，但其在前驱期（轻度认知障碍[MCI]）应用于临床实践的成熟度尚不清楚。在此，我们根据生物标志物开发的五阶段框架，评估脑脊液（CSF）β淀粉样蛋白（Aβ42）、总tau蛋白和磷酸化tau蛋白。关于CSF生物标志物，第1阶段（识别有用线索）和第2阶段（评估AD痴呆与对照的准确性）已有充分证据。第3阶段（在MCI中的效用）已部分实现。在随访时间长的队列中，CSF Aβ42、总tau蛋白和磷酸化tau蛋白对AD所致MCI具有较高的诊断准确性。第4阶段（在现实世界中的表现）正在进行中，第5阶段研究（量化影响和成本）即将开展。我们的结果突出了在临床中应用CSF生物标志物时需要优先考虑并正确使用的事项。优先事项包括通过引入全自动检测系统来减少测量变异性；在MCI阶段提高对非AD神经认知疾病的诊断特异性；以及阐明CSF生物标志物与其他生物标志物模式在临床实践和临床试验设计中的作用。这些工作目前正在进行中。
