Detecting amyloid–β pathology in subjective cognitive decline using plasma and CSF biomarkers

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. FUNDING: The research leading to these results has received funding from the Alzheimer's Drug Discovery Foundation (ADDF) grants #RDADB-201906-2018897 and #201809-2016862. Additionally, the study has been funded by the Health Department of the Catalan Government, the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Grant agreement No. 948677), and PI22/00456, funded by Instituto de Salud Carlos III (ISCIII).

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Publication Details

Journal
EBioMedicine
Published
2026-06-16
DOI
https://doi.org/10.1016/j.ebiom.2026.106331
Primary Topic
Dementia and Cognitive Impairment Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Detecting amyloid–β pathology in subjective cognitive decline using plasma and CSF biomarkers

Esther Jimenez Moyano, Karine Fauria, Federico Emanuele Pozzi, Aitana Plaza Raimundo et al.
EBioMedicine
Dementia and Cognitive Impairment Research
article

Detecting amyloid–β pathology in subjective cognitive decline using plasma and CSF biomarkers

Esther Jimenez Moyano, Karine Fauria, Federico Emanuele Pozzi, Aitana Plaza Raimundo, Anna Brugulat Serrat, José Contador, Armand González‐Escalante, Gonzalo Sánchez‐Benavides, Juan Lantero‐Rodriguez, Sherezade Fuentes, Paula Marne, Raffaele Cacciaglia, Nathalie Le Bastard, Jordi Huguet, Gemma Salvadó, Marc Vilanova, Laia Montoliu‐Gaya, Javier Torres‐Torronteras, Andreas Jeromin, Ruth Dominguez, Ana Fernández‐Arcos, L. Solsona, Oriol Grau‐Rivera, Gwendlyn Kollmorgen, Eugeen Vanmechelen, Marc Suárez‐Calvet, Carme Deulofeu, David López‐Martos, Annabella B Gorriti, Lidia C Gispert, Aida Fernández Lebrero, Clara Quijano‐Rubio, Anna S Prat, José Luis Molinuevo, A Ballester, Laura H Penas, Pau Sanchez, C. Rodríguez, Alícia Nadal, Helena Blasco‐Forniés, Marta del Campo, Iva Knezevic, Alba Cañas, Marina de Diego-Osaba, Paula Ortiz-Romero, Henrik Zetterberg, Jordi Freixa, Carolina Minguillon, Fernanda Campos Strazzi, David Vallez, Xavier Meléndez Giner, Montserrat Vilà Farrés, Irene Navalpotro Gómez, Maria Roman Cabiscol, Maria Emilio Pascual, Neus De la Cruz-Sánchez Badia, Nicholas J. Ashton, Kaj Blennow, Laura Gusó, Isabel Estragués Gazquez, Mireia Sánchez Gutiérrez, Juan Domingo Gispert, Elisabeth Ferrer i Mairal
article en

Abstract

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. FUNDING: The research leading to these results has received funding from the Alzheimer's Drug Discovery Foundation (ADDF) grants #RDADB-201906-2018897 and #201809-2016862. Additionally, the study has been funded by the Health Department of the Catalan Government, the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Grant agreement No. 948677), and PI22/00456, funded by Instituto de Salud Carlos III (ISCIII).

EBioMedicineVol. 129
Roche (Switzerland) (CH), Universidad San Pablo CEU (ES), Cornell University (US), Sahlgrenska University Hospital (SE), Sorbonne Université (FR), Roche Pharma AG (Germany) (DE), Pasqual Maragall Foundation (ES), Structural Analytics (United States) (US), UK Dementia Research Institute (GB), Hospital Del Mar (ES), Catalonian Research and Innovation Centre (ES), Banner Sun Health Research Institute (US), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (ES), ADx NeuroSciences, University College London (GB), Fujirebio (Belgium) (BE), University of Milano-Bicocca (IT)
Alzheimer's Drug Discovery Foundation, European Commission, Hjärnfonden, Vetenskapsrådet, Instituto de Salud Carlos III, Departament de Salut, Generalitat de Catalunya, H2020 European Research Council
Openalex Percentile: Top 7%
Dementia and Cognitive Impairment Research
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