Detecting amyloid-β pathology in subjective cognitive decline using plasma and CSF biomarkers
EBioMedicine
Contador J, Pozzi FE, Sánchez-Benavides G, Fernández-Arcos A, Lantero-Rodríguez J, Montoliu-Gaya L, Minguillon C, Fauria K, González-Escalante A, Ortiz-Romero P, Blasco-Forniés H, de Diego-Osaba M, Jiménez Moyano E, Quijano-Rubio C, Kollmorgen G, Le Bastard N, Nadal A, Vanmechelen E, Jeromin A, Torres-Torronteras J, Ashton NJ, Zetterberg H, Blennow K, Gispert JD, Molinuevo JL, Del Campo M, Grau-Rivera O, Suárez-Calvet M; β-AARC Study collaborators.
Resumen
Background: Subjective cognitive decline (SCD) may represent an early stage of Alzheimer's disease (AD), but biomarker studies in this population are limited. Therefore, we compared the performance of a comprehensive panel of novel cerebrospinal fluid (CSF) and blood biomarkers across different platforms for detecting amyloid-β (Aβ) pathology in SCD.
Methods: 143 individuals with SCD (20% Aβ-positive) from the β-AARC cohort were included. Aβ status was determined by CSF Aβ42/40. CSF and blood biomarkers of Aβ, tau, synaptic function, neurodegeneration, and glial reactivity were measured cross-sectionally.
Findings: In CSF, novel tau variants (p-tau205, p-tau217, p-tau231, p-tau235, NTA-tau) were elevated in Aβ-positive individuals with SCD. In plasma, p-tau217, p-tau217/Aβ42 (across multiple platforms), as well as p-tau181, p-tau181/Aβ42 and Aβ42/40 (platform-dependent) demonstrated strong discriminatory performance and high negative predictive value, but limited positive predictive value because of the low prevalence of Aβ pathology.
Interpretation: In conclusion, several plasma biomarkers can exclude Aβ pathology in SCD, while some CSF and plasma markers indicate early AD-related changes. These plasma biomarkers could serve as accessible, cost-effective tools for early AD detection and risk stratification, and expedite the selection of candidates for disease-modifying treatments or preventive strategies.
