Nature Communications: Streamlined Alzheimer's Biomarker Assay
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.
Investigators from Pitt Psychiatry including Yijun Chen, PhD (prior graduate student, Karikari Lab); Chaeryon Kang, PhD (Associate Professor of Psychiatry and Biostatistics); Tharick Pascoal, MD, PhD (Associate Professor of Psychiatry and Neurology); Victor Villemagne, MD (Levidow-Pittsburgh Foundation Chair in Alzheimer's Disease and Dementia Disorders and Professor of Psychiatry); and Ann Cohen, PhD (Associate Professor of Psychiatry), and led by Thomas Karikari, PhD (Associate Professor of Psychiatry and Clinical and Translational Science), adopted current techniques to create an enhanced IP-MS method. The streamlined PAβ V2.0 assay is designed to be run on a cost-effective table-top mass spectrometry instrument. It decreases sample preparation time and pre-analytical processing steps, reduces sample volume requirements, and records superior clinical accuracies compared with existing immunoassays alternatives.
Results from the improved assay, recently published in Nature Communications, revealed excellent dilution linearity, high precision, enhanced sensitivity, improved Aβ recovery, and markedly increased signal-to-noise ratios. In a cohort of cognitively unaffected older adults, the plasma Aβ1-42/Aβ1-40 ratio achieved stronger concordance with Aβ-PET and superior accuracies to identify abnormal scans. Notably, demonstrated superior clinical performance was observed even with plasma volumes as low as 100 μL.
“Mass spectrometry remains the method of choice for measuring Aβ peptides in blood. Our streamlined method addresses the challenges of existing methods, thereby enabling higher throughput and increased productivity for large scale clinical and research applications,” said Dr. Karikari, senior author of the study.
Chen Y, Zeng X, Olvera-Rojas M, Sewell KR, Sehrawat A, Gu J, Triviño-Ibañez EM, Solis-Urra P, Gómez- Río M, Oberlin LE, Kramer AF, Hillman CH, Burns JM, Marsland AL, Kang C, McAuley E, Ikonomovic MD, Pascoal TA, Villemagne VL, Lopez OL, Cohen AD, Esteban-Cornejo I, Yates NA, Erickson KI, Karikari TK.
Nature Communications 17, 1673 (2026). https://doi.org/10.1038/s41467-026-68372-w