Journal article
Streamlined resource-efficient plasma amyloid-beta mass spectrometry assay has improved biomarker performance in preclinical Alzheimer's disease
Nature communications, Vol.17(1), 1673
2026
PMID: 41571708
Abstract
Plasma amyloid-β (Aβ) peptides, alone or in ratio with p-tau217, show strong potential as Alzheimer's disease biomarkers. While immunoprecipitation-mass spectrometry (IP-MS) is the preferred method for plasma Aβ quantification, current assays are resource- and time-intensive. Here, we developed a streamlined IP-MS method using a cost-effective instrument that significantly improved the efficiency of an original assay by incorporating a single immunoprecipitation step, an optimized buffer system, and approximately 75% reductions in antibody and sample volume requirements. Technical validation revealed excellent dilution linearity (r²>0.99), high precision (< 10% variation), enhanced sensitivity, improved Aβ recovery, and markedly increased signal-to-noise ratios. In a large cohort of cognitively normal older adults (n = 317), the plasma Aβ1-42/Aβ1-40 ratio achieved stronger concordance with Aβ-PET and superior accuracies to identify abnormal scans (AUC 0.81 vs. 0.65 for the original assay). Notably, accuracies remained high even with plasma volumes as low as 100 μL. The improved IP-MS method enables robust and simplified plasma Aβ assessment in Alzheimer's disease, with implications for prognosis, diagnosis and intervention trials.
Details
- Title
- Streamlined resource-efficient plasma amyloid-beta mass spectrometry assay has improved biomarker performance in preclinical Alzheimer's disease
- Authors/Creators
- Yijun Chen - University of PittsburghXuemei Zeng - University of PittsburghMarcos Olvera-Rojas - Universidad de GranadaKelsey R Sewell - Murdoch UniversityAnuradha Sehrawat - University of PittsburghJeremy Gu - University of PittsburghEva María Triviño-Ibañez - Instituto de Investigación Biosanitaria de GranadaPatricio Solis-Urra - Universidad Andrés BelloManuel Gómez-Río - Instituto de Investigación Biosanitaria de GranadaLauren E Oberlin - Weill Cornell MedicineArthur F Kramer - University of Illinois Urbana-ChampaignCharles H Hillman - Northeastern UniversityJeffrey M Burns - University of KansasAnna L Marsland - University of PittsburghChaeryon Kang - University of PittsburghEdward McAuley - University of Illinois Urbana-ChampaignMilos D Ikonomovic - University of PittsburghTharick A Pascoal - University of PittsburghVictor L Villemagne - University of PittsburghOscar L Lopez - University of PittsburghAnn D Cohen - University of PittsburghIrene Esteban-Cornejo - Universidad de GranadaNathan A Yates - University of PittsburghKirk I Erickson - Translational Research Institute for Metabolism and DiabetesThomas K Karikari - University of Pittsburgh
- Publication Details
- Nature communications, Vol.17(1), 1673
- Grant note
- P01 AG025204 / NIA NIH HHS P30 AG066468 / NIA NIH HHS K23 MH129882 / NIMH NIH HHS R01 AG083874 / NIA NIH HHS
- Identifiers
- 991005884845607891
- Copyright
- © The Author(s) 2026
- Murdoch Affiliation
- School of Psychology
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: SDGs in the Output
Metrics
1 Record Views