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一项多中心研究中脑脊液生物标志物与淀粉样蛋白PET的一致性

Agreement of cerebrospinal fluid biomarkers and amyloid-PET in a multicenter study.

作者信息

Guillén Núria, Contador José, Buongiorno Mariateresa, Álvarez Ignacio, Culell Natalia, Alcolea Daniel, Lleó Alberto, Fortea Juan, Piñol-Ripoll Gerard, Carnes-Vendrell Anna, Lourdes Ispierto María, Vilas Dolores, Puig-Pijoan Albert, Fernández-Lebrero Aida, Balasa Mircea, Sánchez-Valle Raquel, Lladó Albert

机构信息

Alzheimer's Disease and Other Cognitive Disorders Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Carrer Villarroel, 170, 08036, Barcelona, Spain.

Memory Disorders Unit, Department of Neurology, Hospital Universitari Mutua de Terrassa, Terrassa, Spain.

出版信息

Eur Arch Psychiatry Clin Neurosci. 2025 Feb;275(1):257-266. doi: 10.1007/s00406-023-01701-y. Epub 2023 Oct 28.

Abstract

Core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers have shown incomplete agreement with amyloid-positron emission tomography (PET). Our goal was to analyze the agreement between AD CSF biomarkers and amyloid-PET in a multicenter study. Retrospective multicenter study (5 centers). Participants who underwent both CSF biomarkers and amyloid-PET scan within 18 months were included. Clinical diagnoses were made according to latest diagnostic criteria by the attending clinicians. CSF Amyloid Beta (Aβ, A), phosphorliated tau 181 (pTau181, T) and total tau (tTau, N) biomarkers were considered normal (-) or abnormal ( +) according to cutoffs of each center. Amyloid-PET was visually classified as positive/negative. Agreement between CSF biomarkers and amyloid-PET was analyzed by overall percent agreement (OPA). 236 participants were included (mean age 67.9 years (SD 9.1), MMSE score 24.5 (SD 4.1)). Diagnoses were mild cognitive impairment or dementia due to AD (49%), Lewy body dementia (22%), frontotemporal dementia (10%) and others (19%). Mean time between tests was 5.1 months (SD 4.1). OPA between single CSF biomarkers and amyloid-PET was 74% for , 75% for pTau181, 73% for tTau. The use of biomarker ratios improved OPA: 87% for Aβ/Aβ (n = 155), 88% for pTau181/Aβ (n = 94) and 82% for tTau/Aβ (n = 160). A + T + N + cases showed the highest agreement between CSF biomarkers and amyloid-PET (96%), followed by A-T-N- cases (89%). Aβ/Aβ was a better marker of cerebral amyloid deposition, as identified by amyloid tracers, than Aβ alone. Combined biomarkers in CSF predicted amyloid-PET result better than single biomarkers.

摘要

核心阿尔茨海默病(AD)脑脊液(CSF)生物标志物与淀粉样蛋白正电子发射断层扫描(PET)结果不完全一致。我们的目标是在一项多中心研究中分析AD脑脊液生物标志物与淀粉样蛋白PET之间的一致性。回顾性多中心研究(5个中心)。纳入在18个月内同时接受脑脊液生物标志物检测和淀粉样蛋白PET扫描的参与者。临床诊断由主治医生根据最新诊断标准做出。脑脊液淀粉样β蛋白(Aβ,A)、磷酸化tau蛋白181(pTau181,T)和总tau蛋白(tTau,N)生物标志物根据各中心的临界值被视为正常(-)或异常(+)。淀粉样蛋白PET在视觉上被分类为阳性/阴性。通过总体一致百分比(OPA)分析脑脊液生物标志物与淀粉样蛋白PET之间的一致性。纳入了236名参与者(平均年龄67.9岁(标准差9.1),简易精神状态检查表(MMSE)评分24.5(标准差4.1))。诊断为因AD导致的轻度认知障碍或痴呆(49%)、路易体痴呆(22%)、额颞叶痴呆(10%)和其他(19%)。两次检测之间的平均时间为5.1个月(标准差4.1)。单个脑脊液生物标志物与淀粉样蛋白PET之间的OPA,Aβ为74%,pTau181为75%,tTau为73%。使用生物标志物比值提高了OPA:Aβ/Aβ为87%(n = 155),pTau181/Aβ为88%(n = 94),tTau/Aβ为82%(n = 160)。A+T+N+病例在脑脊液生物标志物与淀粉样蛋白PET之间显示出最高的一致性(96%),其次是A-T-N-病例(89%)。与单独的Aβ相比,Aβ/Aβ作为由淀粉样蛋白示踪剂确定的脑淀粉样蛋白沉积的标志物更好。脑脊液中的联合生物标志物比单个生物标志物能更好地预测淀粉样蛋白PET结果。

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