Clinical performance of an antibody-free assay for plasma A[beta]42/A[beta]40 to detect early alterations of Alzheimer's disease in individuals with subjective cognitive decline

• Published in: Alzheimer's research & therapy 2023-01, Vol.15 (1)
• Main Authors: Sarasa, Leticia, Sarasa, Manuel, Orellana, A, Bullich, S, Muéoz, N, Caéada, L, Vargas, L, Pytel, V, Sanabria, Ãngela, Hernández, I, Torres, M, Gailhajenet, A, Ruíz, Agustín, Bojayrin, U, Lomeéa, F, Seguer, S, Morera, A, Giménez, J, Nogales, A. B, Ortega, G, Ricciardi, M, Perissinotti, A, García, P, Pancho, A, Esteban-De Antonio, E, García-Sánchez, A, Pelejà, E, Sotolongo-Grau, O, Páez, A, Lafuente, A, Marquié, Marta, Valero, S, Guitart, M, Núéez, L, Gómez-Chiari, M, Diego, S, Tejero, M. A, Moreno, M, Montrreal, L, Pérez-Cordon, A, Pascual-Lucas, María, Terencio, Jose, Boada, Mercè, Martín, E, Preckler, S, Aguilera, N, Stephens, A, Espinosa, A, Buendia, M, Alarcón-Martín, E, Castillo, Sergio, Roé-Vellvé, N, Pérez, E, Ramis, M. I, Rosende-Roca, M, Tartari, Juan Pablo, Jang, Hyemin, Campos, F, Lleonart, N, Caéabate, P, Tárraga, Lluís, Niéerola, A, Vivas, A, Ibarria, M, Allué, José Antonio, Fandos, Noelia, Seo, Sang Won, Narvaiza, L, Rodríguez-Gomez, O, Cano, A, Alegret, M, Cuevas, C, de Rojas, I, Berthier, M, Alonso-Lana, S
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amyloid beta-protein; Blood; Development and progression; Diagnosis; Health aspects; Mass spectrometry; Measurement; Medical examination; Methods
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-022-01143-z

Background 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 (A[beta])42/A[beta]40 ratio measured by an antibody-free mass-spectrometric (MS) method, ABtest-MS, to detect early pathological changes of AD. Methods This cohort study included data from the baseline and 2-year follow-up visits from the Fundació ACE Healthy Brain Initiative (FACEHBI) study. Plasma A[beta]42/A[beta]40 was measured with ABtest-MS and compared to .sup.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 A[beta]42/A[beta]40 with episodic memory performance and brain atrophy were assessed. Results The FACEHBI cohort at baseline included 200 healthy individuals with subjective cognitive decline (SCD), of which 36 (18%) were A[beta]-PET positive. Plasma A[beta]42/A[beta]40 levels were significantly lower in A[beta]-PET positive individuals (median [interquartile range, IQR], 0.215 [0.203-0.236]) versus A[beta]-PET negative subjects (median [IQR], 0.261 [0.244-0.279]) (P < .001). Plasma A[beta]42/A[beta]40 was significantly correlated with A[beta]-PET levels (rho = -0.390; P < .001) and identified A[beta]-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 A[beta]42/A[beta]40 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 A[beta]42/A[beta]40 ratio was associated with worse episodic memory performance and increased brain atrophy. Plasma A[beta]42/A[beta]40 at baseline predicted clinical conversion to mild cognitive impairment and longitudinal changes in amyloid deposition and brain atrophy at 2-year follow-up. Conclusions This study suggests that plasma A[beta]42/A[beta]40, 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. Keywords: Alzheimer's disease, Amyloid, A[beta]42/A[beta]40, Ratio, Biomarkers, Pla