多重脑脊液蛋白质组学鉴定出用于阿尔茨海默病诊断和预测的生物标志物。
Multiplex cerebrospinal fluid proteomics identifies biomarkers for diagnosis and prediction of Alzheimer's disease.
机构信息
Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
出版信息
Nat Hum Behav. 2024 Oct;8(10):2047-2066. doi: 10.1038/s41562-024-01924-6. Epub 2024 Jul 10.
Recent expansion of proteomic coverage opens unparalleled avenues to unveil new biomarkers of Alzheimer's disease (AD). Among 6,361 cerebrospinal fluid (CSF) proteins analysed from the ADNI database, YWHAG performed best in diagnosing both biologically (AUC = 0.969) and clinically (AUC = 0.857) defined AD. Four- (YWHAG, SMOC1, PIGR and TMOD2) and five- (ACHE, YWHAG, PCSK1, MMP10 and IRF1) protein panels greatly improved the accuracy to 0.987 and 0.975, respectively. Their superior performance was validated in an independent external cohort and in discriminating autopsy-confirmed AD versus non-AD, rivalling even canonical CSF ATN biomarkers. Moreover, they effectively predicted the clinical progression to AD dementia and were strongly associated with AD core biomarkers and cognitive decline. Synaptic, neurogenic and infectious pathways were enriched in distinct AD stages. Mendelian randomization did not support the significant genetic link between CSF proteins and AD. Our findings revealed promising high-performance biomarkers for AD diagnosis and prediction, with implications for clinical trials targeting different pathomechanisms.
最近蛋白质组学覆盖范围的扩大为揭示阿尔茨海默病（AD）的新生物标志物开辟了前所未有的途径。在 ADNI 数据库中分析的 6361 种脑脊液（CSF）蛋白中，YWHAG 在诊断生物学上（AUC=0.969）和临床上（AUC=0.857）定义的 AD 方面表现最佳。四个（YWHAG、SMOC1、PIGR 和 TMOD2）和五个（ACHE、YWHAG、PCSK1、MMP10 和 IRF1）蛋白组极大地提高了准确性，分别达到 0.987 和 0.975。它们在独立的外部队列和区分尸检证实的 AD 与非 AD 方面的优异性能得到了验证，甚至可以与经典的 CSF ATN 生物标志物相媲美。此外，它们有效地预测了向 AD 痴呆的临床进展，并且与 AD 的核心生物标志物和认知能力下降密切相关。在不同的 AD 阶段，突触、神经发生和感染途径得到了丰富。孟德尔随机化不支持 CSF 蛋白与 AD 之间存在显著遗传联系。我们的发现揭示了有希望的 AD 诊断和预测的高性能生物标志物，这对针对不同发病机制的临床试验具有重要意义。
Zotero 插件