背景:越来越多的证据支持使用淀粉样蛋白的血浆生物标志物,tau,神经变性,和神经炎症诊断痴呆。然而,他们在临床中对路易体痴呆(DLB)的阳性和鉴别诊断仍不确定.
方法:我们在两个三级记忆中心进行了一项回顾性生物标志物研究,巴黎Lariboisière和CM2RR斯特拉斯堡,法国,纳入DLB患者(n=104),阿尔茨海默病(AD,n=76),和神经控制(NC,n=27)。测量的生物标志物包括血浆Aβ40/Aβ42比率,p-tau181,NFL,和GFAP使用SIMOA和血浆YKL-40和sTREM2使用ELISA。根据他们的CSFAβ谱对具有可用CSF分析的DLB患者(n=90)进行分层。
结果:DLB患者显示血浆Aβ比值改变,p-tau181和GFAP水平与NC和改良血浆Aβ比率相比,p-tau181,GFAP,NFL,和sTREM2水平与AD患者相比。AD患者的血浆p-tau181最佳分化DLB(ROC分析,曲线下面积[AUC]=0.80)和NC(AUC=0.78),而结合生物标志物并不能改善诊断表现.血浆p-tau181是区分淀粉样蛋白阳性和淀粉样蛋白阴性DLB病例(AUC=0.75)的最佳独立生物标志物,并且与DLB组的认知状态相关。结合血浆Aβ比值,p-tau181和NfL提高了鉴定淀粉样蛋白共病理学的性能(AUC=0.79)。主成分分析确定了DLB和AD组中生物标志物的不同分离模式。
结论:淀粉样蛋白,tau,神经变性和神经炎症血浆生物标志物在DLB中被修饰,尽管具有中等的诊断性能。血浆p-tau181有助于鉴定DLB中的Aβ共形病理学。
BACKGROUND: Increasing evidence supports the use of plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation for diagnosis of dementia. However, their performance for positive and differential diagnosis of dementia with Lewy bodies (DLB) in clinical settings is still uncertain.
METHODS: We conducted a retrospective biomarker study in two tertiary memory centers, Paris Lariboisière and CM2RR Strasbourg, France, enrolling patients with DLB (n = 104), Alzheimer\'s disease (AD, n = 76), and neurological controls (NC, n = 27). Measured biomarkers included plasma Aβ40/Aβ42 ratio, p-tau181, NfL, and GFAP using SIMOA and plasma YKL-40 and sTREM2 using ELISA. DLB patients with available CSF analysis (n = 90) were stratified according to their CSF Aβ profile.
RESULTS: DLB patients displayed modified plasma Aβ ratio, p-tau181, and GFAP levels compared with NC and modified plasma Aβ ratio, p-tau181, GFAP, NfL, and sTREM2 levels compared with AD patients. Plasma p-tau181 best differentiated DLB from AD patients (ROC analysis, area under the curve [AUC] = 0.80) and NC (AUC = 0.78), and combining biomarkers did not improve diagnosis performance. Plasma p-tau181 was the best standalone biomarker to differentiate amyloid-positive from amyloid-negative DLB cases (AUC = 0.75) and was associated with cognitive status in the DLB group. Combining plasma Aβ ratio, p-tau181 and NfL increased performance to identify amyloid copathology (AUC = 0.79). Principal component analysis identified different segregation patterns of biomarkers in the DLB and AD groups.
CONCLUSIONS: Amyloid, tau, neurodegeneration and neuroinflammation plasma biomarkers are modified in DLB, albeit with moderate diagnosis performance. Plasma p-tau181 can contribute to identify Aβ copathology in DLB.