Llorens Franc, Schmitz Matthias, Knipper Tobias, Schmidt Christian, Lange Peter, Fischer Andre, Hermann Peter, Zerr Inga
Department of Neurology, Universitätsmedizin GöttingenGöttingen, Germany.
Center for Networked Biomedical Research on Neurodegenerative DiseasesBarcelona, Spain.
Front Aging Neurosci. 2017 Sep 12;9:289. doi: 10.3389/fnagi.2017.00289. eCollection 2017.
Vascular factors increase the risks of developing Alzheimer's disease (AD) and they contribute to AD pathology. Since amyloid beta (Aβ) deposits can be observed in both diseases, there is an overlap which impedes a clear discrimination and difficult clinical diagnosis. In the present study, we compared cerebrospinal fluid (CSF) profiles of neurodegenerative and inflammatory biomarkers in a patient cohort of controls ( = 50), AD ( = 65) and vascular dementia (VaD) ( = 31) cases. Main results were validated in a second cohort composed of AD ( = 26), rapidly progressive AD (rpAD) ( = 15), VaD ( = 21), and cognitively unimpaired patients with vascular encephalopathy (VE) ( = 25) cases. In the study, cohort significant differences were detected in tau, p-tau, and Aβ1-42 (Aβ42) levels between AD and VaD patients, but not for the neuron-specific enolase (NSE), S100B protein, 14-3-3 and YKL-40. Differential tau, p-tau, and Aβ42 levels between AD and VaD were confirmed in the validation cohort, which additionally showed no differences between AD and rpAD, nor between VaD and VE. The evaluation of the biomarker performance in discrimination between AD and VaD patients revealed that the best diagnostic accuracy could be obtained when tau, p-tau, and Aβ42 were combined in form of Aβ42/p-tau (AUC 0.84-0.90, sensitivity 77-81%, specificity 80-93%) and (tau × p-tau)/Aβ42 ratio (AUC 0.83-0.87, sensitivity 73-81%, specificity 78-87%). Altogether, our studies provided neurodegenerative biomarker profiles in two cohorts of AD and VaD patients favoring the combination of CSF biomarker to differentiate between diseases.
血管因素会增加患阿尔茨海默病(AD)的风险,并促使AD病理形成。由于在这两种疾病中均能观察到β淀粉样蛋白(Aβ)沉积,存在重叠现象,这妨碍了明确区分以及临床诊断的难度。在本研究中,我们比较了对照组(n = 50)、AD患者(n = 65)和血管性痴呆(VaD)患者(n = 31)队列中神经退行性和炎症生物标志物的脑脊液(CSF)特征。主要结果在由AD患者(n = 26)、快速进展性AD(rpAD)患者(n = 15)、VaD患者(n = 21)以及认知未受损的血管性脑病(VE)患者(n = 25)组成的第二个队列中得到验证。在该研究中,检测到AD和VaD患者之间tau、p - tau和Aβ1 - 42(Aβ42)水平存在显著差异,但神经元特异性烯醇化酶(NSE)、S100B蛋白、14 - 3 - 3和YKL - 40水平无差异。AD和VaD之间tau、p - tau和Aβ42水平的差异在验证队列中得到证实,该队列还显示AD和rpAD之间以及VaD和VE之间无差异。对AD和VaD患者鉴别中生物标志物性能的评估表明,当以Aβ42/p - tau形式(曲线下面积0.84 - 0.90,灵敏度77 - 81%,特异性80 - 93%)以及(tau×p - tau)/Aβ42比值(曲线下面积0.83 - 0.87,灵敏度73 - 81%,特异性78 - 87%)组合tau、p - tau和Aβ42时,可获得最佳诊断准确性。总之,我们的研究提供了AD和VaD患者两个队列中的神经退行性生物标志物特征,支持联合脑脊液生物标志物来区分不同疾病。