Clinical performance of an antibody-free assay for plasma Aβ42/Aβ40 to detect early alterations of Alzheimer’s disease in individuals with subjective cognitive decline

四分位间距 队列 医学 内科学 记忆诊所 置信区间 痴呆 认知功能衰退 接收机工作特性 胃肠病学 疾病
作者
María Pascual‐Lucas,José Antonio Allué,Leticia Sarasa,Noelia Fandos,Sergio Castillo,J. Terencio,Manuel Sarasa,Juan Pablo Tartari,Ángela Sanabria,Lluís Tárraga,Agustı́n Ruiz,Marta Marquié,Sang Won Seo,Hyemin Jang,Merçé Boada,N. Aguilera,Emilio Alarcón‐Martín,Montserrat Alegret,Silvia Alonso‐Lana,Marcelo L. Berthier,U. Bojayrin,Mar Buendía,Santiago Bullich,Francisco Campos,Amanda Cano,Pilar Cañabate,L. Cañada,Claudia Cuevas,Itziar de Rojas,S. Diego,Ana Espinosa,Ester Esteban‐De Antonio,A. Gailhajenet,Asunción Garcı́a-Sánchez,Philip Garcia,J.C. Juárez Giménez,Marta Gómez‐Chiari,M. Guitart,Iván Hernández Ramírez,Marta Ibarria,A. Lafuente,Núria Lleonart,F. Lomeña,E. Martín,M. Moreno,A.M. Morera,Laura Montrreal,N. Muñoz,Leire Narvaiza,A. Niñerola,A. B. Nogales,L. Núñez,Adelina Orellana,Gemma Ortega,Antonio Páez,Ana Pancho,E. Pelejà,Elsa Pérez,Alba Pérez‐Cordón,Andrés Perissinotti,Sílvia Preckler,Vanesa Pytel,Mario Ricciardi,Octavio Rodríguez‐Gómez,Núria Roé-Vellvé,Maribel Ramis,Maitée Rosende‐Roca,S. Seguer,Óscar Sotolongo‐Grau,Andrew Stephens,Miguel Ángel Tejero,M.D. Martínez del Valle Torres,Sergi Valero,Luis Vargas,Assumpta Vivas
出处
期刊:Alzheimer's Research & Therapy [BioMed Central]
卷期号:15 (1) 被引量:25
标识
DOI:10.1186/s13195-022-01143-z
摘要

Accessible and cost-effective diagnostic tools are urgently needed to accurately quantify blood biomarkers to support early diagnosis of Alzheimer's disease (AD). In this study, we investigated the ability of plasma amyloid-beta (Aβ)42/Aβ40 ratio measured by an antibody-free mass-spectrometric (MS) method, ABtest-MS, to detect early pathological changes of AD.This cohort study included data from the baseline and 2-year follow-up visits from the Fundació ACE Healthy Brain Initiative (FACEHBI) study. Plasma Aβ42/Aβ40 was measured with ABtest-MS and compared to 18F-Florbetaben PET as the reference standard (cutoff for early amyloid deposition of 13.5 centiloids). Cross-validation was performed in an independent DPUK-Korean cohort. Additionally, associations of plasma Aβ42/Aβ40 with episodic memory performance and brain atrophy were assessed.The FACEHBI cohort at baseline included 200 healthy individuals with subjective cognitive decline (SCD), of which 36 (18%) were Aβ-PET positive. Plasma Aβ42/Aβ40 levels were significantly lower in Aβ-PET positive individuals (median [interquartile range, IQR], 0.215 [0.203-0.236]) versus Aβ-PET negative subjects (median [IQR], 0.261 [0.244-0.279]) (P < .001). Plasma Aβ42/Aβ40 was significantly correlated with Aβ-PET levels (rho = -0.390; P < .001) and identified Aβ-PET status with an area under the receiver operating characteristic curve (AUC) of 0.87 (95% confidence interval [CI], 0.80-0.93). A cutoff for the Aβ42/Aβ40 ratio of 0.241 (maximum Youden index) yielded a sensitivity of 86.1% and a specificity of 80.5%. These findings were cross-validated in an independent DPUK-Korean cohort (AUC 0.86 [95% CI 0.77-0.95]). Lower plasma Aβ42/Aβ40 ratio was associated with worse episodic memory performance and increased brain atrophy. Plasma Aβ42/Aβ40 at baseline predicted clinical conversion to mild cognitive impairment and longitudinal changes in amyloid deposition and brain atrophy at 2-year follow-up.This study suggests that plasma Aβ42/Aβ40, as determined by this MS-based assay, has potential value as an accurate and cost-effective tool to identify individuals in the earliest stages of AD, supporting its implementation in clinical trials, preventative strategies and clinical practice.
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