Diagnostic Accuracy of Blood-Based Biomarkers for Early Detection of Alzheimer’s Disease: A Systematic Review

Auteurs

  • Cindy Permata Sari Universitas Pelita Harapan
  • Rocksy Fransiska V. Situmeang Universitas Pelita Harapan
  • Tandry Meriyanti Universitas Pelita Harapan

DOI:

https://doi.org/10.19166/lijn.v2i1.11078

Trefwoorden:

Alzheimer’s disease, P-tau217, Blood-based Biomarkers, Early Detection, Diagnostic Accuracy

Samenvatting

Introduction: Alzheimer’s disease (AD) continues to impose a significant global health burden, while early detection remains limited by the reliance on invasive and costly diagnostic methods such as PET imaging and cerebrospinal fluid (CSF) analysis. Blood-based biomarkers have gained attention as a more accessible alternative. This study aims to assess the diagnostic performance of plasma p-tau217, p-tau181, and Aβ42/40 in detecting early-stage AD.

Methods: A systematic review was conducted using predefined inclusion criteria. Studies were selected if they evaluated plasma biomarkers against established reference standards (CSF biomarkers, PET imaging, or neuropathology), reported diagnostic accuracy measures, and included individuals with early cognitive impairment. Extracted data covered study characteristics, assay methods, population profiles, cutoff approaches, and longitudinal outcomes.

Results: Seventeen studies involving more than 7,000 participants were included. Plasma p-tau217 consistently demonstrated the highest diagnostic accuracy across studies, with AUC values generally exceeding 0.90. Plasma p-tau181 also showed good diagnostic performance but with greater variability, particularly in early disease stages. In contrast, Aβ42/40 alone exhibited lower and less consistent accuracy, although its performance improved when combined with phosphorylated tau biomarkers. Variability in assay platforms, population characteristics, and cutoff values contributed to heterogeneity across studies.

Conclusions: Plasma p-tau217 shows strong and consistent diagnostic performance across different populations and settings, approaching that of CSF and PET biomarkers. It holds considerable potential as a practical and minimally invasive tool for early AD detection, although further standardization is still needed.

Keywords: Alzheimer’s Disease, P-tau217, Blood-based Biomarkers, Early Detection, Diagnostic Accuracy

Referenties

1. Palmqvist S, Tideman P, Mattsson-Carlgren N, et al. Palmqvist S, Tideman P, Mattsson-Carlgren N, Schindler SE, Smith R, Ossenkoppele R, et al. Blood biomarkers to detect Alzheimer disease in primary care and secondary care. JAMA. 2024;332(15):1245–1257. https://doi.org/10.1001/jama.2024.13855.

2. Janelidze S, Bali D, Ashton NJ, Barthélemy NR, Vanbrabant J, Stoops E, et al. Head-to-head comparison of 10 plasma phospho-tau assays in prodromal Alzheimer’s disease. Brain. 2023;146(4):1592–1601. https://doi.org/10.1093/brain/awac33.

3. Palmqvist S, Janelidze S, Quiroz YT, Zetterberg H, Lopera F, Stomrud E, et al. Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders. JAMA. 2020;324(8):772–781. https://doi.org/10.1001/jama.2020.12134.

4. Meyer MR, Kirmess KM, Eastwood S, Wente-Roth TL, Irvin F, Holubasch MS, et al. Clinical validation of the PrecivityAD2 blood test: a mass spectrometry-based test with algorithm combining %p-tau217 and Aβ42/40 ratio to identify presence of brain amyloid. Alzheimers Dement. 2024. https://doi.org/10.1002/alz.13764.

5. Wang J, Huang S, Lan G, Lai YJ, Wang QH, Chen Y, et al. Diagnostic accuracy of plasma p-tau217/Aβ42 for Alzheimer’s disease in clinical and community cohorts. Alzheimers Dement. 2025. https://doi.org/10.1002/alz.70038.

6. Barthélemy NR, Horie K, Sato C, Bateman RJ. Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer’s disease. J Exp Med. 2020;217(11):e20200861. https://doi.org/10.1084/jem.20200861

7. Schindler SE, Petersen KK, Saef B, Tosun D, Shaw LM, Zetterberg H, et al. Head-to-head comparison of leading blood tests for Alzheimer’s disease pathology. Alzheimers Dement. 2024. https://doi.org/10.1101/2024.06.12.24308839.

8. Kubota M, Bun S, Takahata K, Kurose S, Momota Y, Iwabuchi Y, et al. Plasma biomarkers for early detection of Alzheimer’s disease: a cross-sectional study in a Japanese cohort. Alzheimers Res Ther. 2025;17:131. https://doi.org/10.1186/s13195-025-01778-8.

9. Wang Y, Cui L, Pan FF, Zhang Z, Huang L, Miao Y, et al. Validation of the robustness of blood-based biomarkers for predicting amyloid-β positivity in Chinese populations. Front Aging Neurosci. 2025. https://doi.org/10.3389/fnagi.2025.1660755.

10. Jiao B, Ouyang Z, Liu Y, Zhang C, Xu T, Yang Q, et al. Evaluating the diagnostic performance of six plasma biomarkers for Alzheimer’s disease and other neurodegenerative dementias in a large Chinese cohort. Alzheimers Res Ther.2025;17:71. https://doi.org/10.1186/s13195-025-01712-y.

11. Ashton NJ, Brum WS, Di Molfetta G, Benedet AL, Arslan B, Jonaitis E, et al. Diagnostic accuracy of a plasma phosphorylated tau 217 immunoassay for Alzheimer disease pathology. JAMA Neurol. 2024;81(3):255–263. https://doi.org/10.1001/jamaneurol.2023.5319.

12. Um YH, Wynveen P, Holland M, Bhatt K, Vucetic Z, Engel B, et al. Neuroimaging correlates and biomarker performance of a fully automated plasma p-tau217/Aβ42 ratio assay in a clinical cohort with Alzheimer’s disease. Alzheimers Dement.2025. https://doi.org/10.1002/alz.70942.

13. Brickman AM, Manly JJ, Honig LS, Sanchez D, Reyes-Dumeyer D, Lantigua RA, et al. Plasma p-tau181, p-tau217, and other blood-based Alzheimer’s disease biomarkers in a multi-ethnic, community study. Alzheimers Dement. 2021. https://doi.org/10.1002/alz.12301.

14. Sehrawat A, Zeng X, Abrahamson EE, Deek RA, Gogola A, Kamboh MI, et al. Pittsburgh plasma p-tau217: classification accuracies for autosomal dominant and sporadic Alzheimer’s disease in the community. Alzheimers Dement. 2025. https://doi.org/10.1002/alz.70409.

15. Mattsson-Carlgren N, Janelidze S, Palmqvist S, Cullen N, Svenningsson AL, Strandberg O, et al. Longitudinal plasma p-tau217 is increased in early stages of Alzheimer’s disease. Brain. 2020;143:3234–3241. https://doi.org/10.1093/brain/awaa286.

16. Thijssen EH, La Joie R, Strom A, Fonseca C, Iaccarino L, Wolf A, et al. Association of plasma p-tau217 and p-tau181 with clinical phenotype, neuropathology, and imaging markers in Alzheimer’s disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study. Lancet Neurol. 2021;20(9):739–752. https://doi.org/10.1016/S1474-4422(21)00214-3.

17. Therriault J, Ashton NJ, Pola I, Triana-Baltzer G, Brum WS, Di Molfetta G, et al. Comparison of two plasma p-tau217 assays to detect and monitor Alzheimer’s pathology. Ebiomedicine. 2024;102:105046. https://doi.org/10.1016/j.ebiom.2024.105046.

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Gepubliceerd

2026-04-30

Citeerhulp

Cindy Permata Sari, Situmeang, R. F. V., & Meriyanti, T. (2026). Diagnostic Accuracy of Blood-Based Biomarkers for Early Detection of Alzheimer’s Disease: A Systematic Review. Lumina : Indonesian Journal of Neurology, 2(1), 29–51. https://doi.org/10.19166/lijn.v2i1.11078