AP-HP Nord, Cognitive Neurology Center Hôpital Lariboisière-Fernand Widal, Université Paris Cité, 200 rue du Faubourg Saint-Denis, Paris, 75010, France.
Université Paris Cité, INSERM, UMRS 1144, Paris, France.
Alzheimers Res Ther. 2024 Jul 3;16(1):146. doi: 10.1186/s13195-024-01502-y.
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.
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.
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.
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.
越来越多的证据支持使用淀粉样蛋白、tau、神经退行性变和神经炎症的血浆生物标志物来诊断痴呆症。然而，它们在临床环境中对路易体痴呆症（DLB）的阳性和鉴别诊断的性能仍不确定。
我们在法国巴黎拉罗什里博瓦西埃和斯特拉斯堡 CM2RR 两个三级记忆中心进行了一项回顾性生物标志物研究，共纳入了 104 例 DLB 患者、76 例阿尔茨海默病（AD）患者和 27 例神经科对照组患者。使用 SIMOA 测量了血浆 Aβ40/Aβ42 比值、p-tau181、NfL 和 GFAP，使用 ELISA 测量了血浆 YKL-40 和 sTREM2。对有脑脊液分析（n=90）的 DLB 患者根据脑脊液 Aβ 谱进行分层。
与 NC 组相比，DLB 患者的血浆 Aβ 比值、p-tau181 和 GFAP 水平发生了改变；与 AD 患者相比，DLB 患者的血浆 Aβ 比值、p-tau181、GFAP、NfL 和 sTREM2 水平发生了改变。血浆 p-tau181 能最好地区分 DLB 与 AD 患者（ROC 分析，曲线下面积[AUC]为 0.80）和 NC（AUC 为 0.78），且联合使用生物标志物并不能提高诊断性能。血浆 p-tau181 是区分淀粉样蛋白阳性和阴性 DLB 病例的最佳独立生物标志物（AUC 为 0.75），且与 DLB 组的认知状态相关。联合使用血浆 Aβ 比值、p-tau181 和 NfL 可以提高识别淀粉样蛋白共病的性能（AUC 为 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。
淀粉样蛋白、tau、神经退行性变和神经炎症的血浆生物标志物在 DLB 中发生了改变，尽管诊断性能中等。血浆 p-tau181 可有助于识别 DLB 中的 Aβ 共病。
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