阿尔茨海默病脑脊液生物标志物与早期病理以及神经元和神经胶质基因表达的改变相关。
Alzheimer's disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression.
作者信息
Ropri Ali S, Lam Tiffany G, Kalia Vrinda, Buchanan Heather M, Bartosch Anne Marie W, Youth Elliot H H, Xiao Harrison, Ross Sophie K, Jain Anu, Chakrabarty Jayanta K, Kang Min Suk, Boyett Deborah, Spinazzi Eleonora F, Iodice Gail, McGovern Robert A, Honig Lawrence S, Brown Lewis M, Miller Gary W, McKhann Guy M, Teich Andrew F
机构信息
Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY 10032, USA.
出版信息
medRxiv. 2024 Jun 13:2024.06.11.24308706. doi: 10.1101/2024.06.11.24308706.
INTRODUCTION
Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early AD pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify CSF biomarkers for AD-related CNS pathophysiologic changes using tissue and fluids with early pathology, free of post-mortem artifact.
METHODS
We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes.
RESULTS
AD pathology on biopsy correlates with CSF β-amyloid-40/42, neurofilament light chain (NfL), and phospho-tau-181(p-tau181)/β-amyloid-42, while several gene expression modules correlate with NfL. Proteomic analysis highlights 7 core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease-relevant groups that correlate with biopsy data..
DISCUSSION
As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking.
引言
接受皮质分流术的正常压力脑积水（NPH）患者在皮质活检时经常显示早期阿尔茨海默病（AD）病理特征，这可预测其进展为临床AD。本研究的目的是利用该队列的样本，通过具有早期病理特征且无尸检假象的组织和液体，识别与AD相关的中枢神经系统（CNS）病理生理变化的脑脊液生物标志物。
方法
我们分析了81例先前记录有病理和转录组变化患者的单分子阵列（Simoa）、蛋白质组学和代谢组学脑脊液数据。
结果
活检时的AD病理与脑脊液β-淀粉样蛋白40/42、神经丝轻链（NfL）以及磷酸化tau-181（p-tau181）/β-淀粉样蛋白42相关，而几个基因表达模块与NfL相关。蛋白质组学分析突出了7种与活检时的病理和基因表达变化相关的核心蛋白，脑脊液的代谢组学分析确定了与活检数据相关的疾病相关组。
讨论
随着更多生物标志物被添加到AD诊断指标中，我们的工作为这些标志物所追踪的CNS病理生理学提供了见解。
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