Mattsson Niklas, Insel Philip S, Palmqvist Sebastian, Portelius Erik, Zetterberg Henrik, Weiner Michael, Blennow Kaj, Hansson Oskar
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden Department of Neurology, Skåne University Hospital, Lund, Sweden
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden Department of Radiology, University of California San Francisco, San Francisco, CA, USA.
EMBO Mol Med. 2016 Oct 4;8(10):1184-1196. doi: 10.15252/emmm.201606540. Print 2016 Oct.
Cerebrospinal fluid (CSF) tau (total tau, T-tau), neurofilament light (NFL), and neurogranin (Ng) are potential biomarkers for neurodegeneration in Alzheimer's disease (AD). It is unknown whether these biomarkers provide similar or complementary information in AD. We examined 93 patients with AD, 187 patients with mild cognitive impairment, and 109 controls. T-tau, Ng, and NFL were all predictors of AD diagnosis. Combinations improved the diagnostic accuracy (AUC 85.5% for T-tau, Ng, and NFL) compared to individual biomarkers (T-tau 80.8%; Ng 71.4%; NFL 77.7%). T-tau and Ng were highly correlated (ρ = 0.79, P < 0.001) and strongly associated with β-amyloid (Aβ) pathology, and with longitudinal deterioration in cognition and brain structure, primarily in people with Aβ pathology. NFL on the other hand was not associated with Aβ pathology and was associated with cognitive decline and brain atrophy independent of Aβ. T-tau, Ng, and NFL provide partly independent information about neuronal injury and may be combined to improve the diagnostic accuracy for AD. T-tau and Ng reflect Aβ-dependent neurodegeneration, while NFL reflects neurodegeneration independently of Aβ pathology.
脑脊液（CSF）中的总tau蛋白（T-tau）、神经丝轻链（NFL）和神经颗粒素（Ng）是阿尔茨海默病（AD）神经退行性变的潜在生物标志物。目前尚不清楚这些生物标志物在AD中提供的是相似信息还是互补信息。我们对93例AD患者、187例轻度认知障碍患者和109名对照者进行了研究。T-tau、Ng和NFL均为AD诊断的预测指标。与单个生物标志物相比，联合使用可提高诊断准确性（T-tau、Ng和NFL联合的曲线下面积为85.5%，T-tau为80.8%；Ng为71.4%；NFL为77.7%）。T-tau和Ng高度相关（ρ = 0.79，P < 0.001），并与β-淀粉样蛋白（Aβ）病理改变以及认知和脑结构的纵向恶化密切相关，主要见于有Aβ病理改变的人群。另一方面，NFL与Aβ病理改变无关，且与认知衰退和脑萎缩相关，独立于Aβ。T-tau、Ng和NFL提供了关于神经元损伤的部分独立信息，可联合使用以提高AD的诊断准确性。T-tau和Ng反映Aβ依赖性神经退行性变，而NFL反映独立于Aβ病理改变的神经退行性变。
