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- Title
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.
- Authors
Pascual-Lucas, María; Allué, José Antonio; Sarasa, Leticia; Fandos, Noelia; Castillo, Sergio; Terencio, Jose; Sarasa, Manuel; Tartari, Juan Pablo; Sanabria, Ángela; Tárraga, Lluís; Ruíz, Agustín; Marquié, Marta; Seo, Sang Won; Jang, Hyemin; Boada, Mercè; on behalf of the FACEHBI study group; Aguilera, N.; Alarcón-Martín, E.; Alegret, M.; Alonso-Lana, S.
- Abstract
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 (Aβ)42/Aβ40 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 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. Results: 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. Conclusions: 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.
- Subjects
ALZHEIMER'S disease; COGNITION disorders; RECEIVER operating characteristic curves; EPISODIC memory; CEREBRAL atrophy; PATHOLOGICAL physiology; MILD cognitive impairment
- Publication
Alzheimer's Research & Therapy, 2023, Vol 15, Issue 1, p1
- ISSN
1758-9193
- Publication type
Article
- DOI
10.1186/s13195-022-01143-z