Aichholzer Freyja, Klafki Hans-Wolfgang, Ogorek Isabella, Vogelgsang Jonathan, Wiltfang Jens, Scherbaum Norbert, Weggen Sascha, Wirths Oliver
Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, Von-Siebold-Str. 5, 37075, Göttingen, Germany.
Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany.
Alzheimers Res Ther. 2021 May 4;13(1):94. doi: 10.1186/s13195-021-00828-1.
Alzheimer's disease (AD) is a neurodegenerative disorder associated with extracellular amyloid-β peptide deposition and progressive neuron loss. Strong evidence supports that neuroinflammatory changes such as the activation of astrocytes and microglia cells are important in the disease process. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a transmembrane glycoprotein that has recently been associated with an emerging role in neuroinflammation, which has been reported to be increased in post-mortem brain samples from AD and Parkinson's disease patients.
The present study describes the partial "fit for purpose" validation of a commercially available immunoassay for the determination of GPNMB levels in the cerebrospinal fluid (CSF). We further assessed the applicability of GPNMB as a potential biomarker for AD in two different cohorts that were defined by biomarker-supported clinical diagnosis or by neuroimaging with amyloid positron emission tomography, respectively.
The results indicated that CSF GPNMB levels could not distinguish between AD or controls with other neurological diseases but correlated with other parameters such as aging and CSF pTau levels.
The findings of this study do not support GPNMB in CSF as a valuable neurochemical diagnostic biomarker of AD but warrant further studies employing healthy control individuals.
阿尔茨海默病(AD)是一种神经退行性疾病,与细胞外淀粉样β肽沉积和进行性神经元丧失有关。有力证据支持,诸如星形胶质细胞和小胶质细胞激活等神经炎症变化在该疾病进程中很重要。糖蛋白非转移性黑色素瘤蛋白B(GPNMB)是一种跨膜糖蛋白,最近被认为在神经炎症中发挥新作用,据报道在AD和帕金森病患者的尸检脑样本中其水平升高。
本研究描述了一种用于测定脑脊液(CSF)中GPNMB水平的市售免疫测定法的部分“适用性”验证。我们进一步在两个分别由生物标志物支持的临床诊断或淀粉样正电子发射断层扫描神经成像定义的不同队列中,评估了GPNMB作为AD潜在生物标志物的适用性。
结果表明,CSF中GPNMB水平无法区分AD患者与患有其他神经系统疾病的对照,但与诸如衰老和CSF中磷酸化tau蛋白(pTau)水平等其他参数相关。
本研究结果不支持CSF中的GPNMB作为AD有价值的神经化学诊断生物标志物,但需要对健康对照个体开展进一步研究。