Plasma Aβ40, Aβ42, Aβ42/40 ratio, tau, p-tau181, p-tau217 and NfL biomarkers to discriminate the prodromal stage of dementia along the continuum of cognitive impairment: Sex differences in the CompAS study

Sep 30, 2026

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Background: Plasma Aβ40, Aβ42, Aβ42/40 ratio, tau, p-tau181, p-tau217, and NfL are proposed as early blood biomarkers for Alzheimer’s disease, yet sex-specific predictive validity remains insufficiently studied. This study cross-sectionally tests biomarker associations to distinguish MCI from preclinical stages (CU, SCD) of the AD continuum in women and men. Method: 145 participants underwent standardized plasma collection and SIMOA quantification. Results: ROC analyses showed significant models only for p-tau181 and p-tau217 overall, with sex-specific validity patterns.

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Abstract

Background

Method

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DOI: 10. 1002/alz70856_104759 BIOMARKERS POSTER PRESENTATION BIOMARKERS (NON-NEUROIMAGING) Plasma Aβ40, Aβ42, Aβ42/40 ratio, tau, p-tau181, p-tau217 and NfL biomarkers to discriminate the prodromal stage of dementia along the continuum of cognitive impairment: Sex differences in the CompAS study Ana I. Rodríguez-Pérez 1, 2, 3 Maria Campos-Magdaleno6, 7 Santiago Galdo-Álvarez9, 10 M. José Moreno-Carretero 11 Juan J. Ansede-Bermejo4, 5 Cristina Lojo-Seoane6, 7, 8 Ana Nieto-Vieites7, 8 Alba Felpete6, 7, 8 Mónica Lindín9, 10 Jose M. Aldrey 12 Águeda Rojo-Pantoja 11 Carlos Spuch 13 Juan M. Pías-Peleteiro 14 Montserrat Zurrón9, 10 Angel Carracedo5, 15 Jose Luis Labandeira 14, 16, 17 David Facal7, 8, 9 Fernando Díaz9, 10 Arturo X. Pereiro Rozas6, 7, 8 1 Centro Singular de Investigación en Medicina Molecular e Enfermidades Cronicas (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain 2 Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Galicia, Spain 3 Centro de investigación Biomédica en Red sobre Enfermedades Neurodegenrativas (CIBERNED), Santiago de Compostela, Gallicia, Spain 4 Centro Nacional de Genotipado (CEGEN-PRB3-ISCIII), Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain 5 Fundación Pública Galega de Medicina Xenómica-CIBERER-IDIS, Santiago de Compostela, Spain 6 Instituto de Psicoloxía (IPsiUS), Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain 7 Departamento de Psicoloxía Evolutiva e da Educación, Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain 8Applied Cognitive Neuroscience and Psychogerontology group, Health Research Abstract Background: Plasma Aβ40, Aβ42, Aβ42/40 ratio, tau, p-tau181, p-tau217, and NfL have been proposed as possible valid early blood biomarkers for Alzheimer’s Dementia (AD) (Simren et al., 2021). Although sex differences in some biomarkers (e.g., p-Tau- 181) were suggested in some studies (Tsiknia et al., 2022), this issue remains largely unexplored. Our aim was cross-sectionally analyze predictive associations of the biomarkers to differentiate MCI from preclinical stages(CU, SCD)oftheAD continuum in both women and men. Method: Sample consisted of 145 participants (CU=20; SCD=57; MCI=68), mostly women (73.7%) and with age media above 70 years (M = 70. 39; SD = 9. 62) (see Table 1 for sample descriptives). Peripheral blood samples drawn into EDTA tubes, centrifuged, and plasma samples aliquoted and kept at –80◦C according to standardized biobanking protocols. Approximately seven months after storage, the concentrations of NfL, Aβ-40, Aβ-42, tau, p-tau217, and p-tau181 were quantified using the ultra-sensitive Single Molecule Array(SIMOA)technology on the Simoa SR-X platform(Quanterix). The corresponding commercial kits (PCs. 104073, 101995, 104570, and 104111) were used in strict accordance with the manufacturer’s protocol. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Alzheimer’s Association. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association. Alzheimer’s Dement. 2025;21(Suppl. 2):e104759. [https://doi.org/10.1002/alz70856_104759](https://doi.org/10.1002/alz70856_104759) wi[leyonlinelibrary.com/journal/alz](leyonlinelibrary.com/journal/alz) 1of4 BIOMARKERS Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain 9 Instituto de Psicoloxía (IPsiUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain 10 Universidade de Santiago de Compostela, Santiago de Compostela, Spain 11 Galicia Sur Health Research Institute (IISGS), Vigo, Pontevedra, Spain 12 Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spa

FAQs

What was the study’s main objective?

To analyze cross-sectional predictive associations of plasma biomarkers to differentiate MCI from preclinical AD stages (CU, SCD) in both women and men.

Which plasma biomarkers were measured?

NfL, Aβ-40, Aβ-42, tau, p-tau217, and p-tau181 were quantified from peripheral blood plasma using ultra-sensitive SIMOA technology.

What did ROC results show regarding sex differences?

Significant ROC models were found only for p-tau181 and p-tau217 overall; p-tau217 was valid for women and men, while predictive significance and classification accuracy differed between women and men.

Sep 30, 2026

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