Streamlined resource-efficient plasma amyloid-beta mass spectrometry assay has improved biomarker performance in preclinical Alzheimer’s disease
Year: 2026
Type: article
Abstract: High-performance, resource-efficient methods for plasma amyloid-β (Aβ) quantification in Alzheimer’s disease are lacking; existing mass spectrometry-based assays are resource- and time-intensive. We developed a streamlined mass spectrometry method with a single immunoprecipitation step, an optimized buffer system, and ≤75% less antibody requirement. Analytical and clinical performances were compared with an in-house reproduced version of a well-known two-step assay. The streamlined assay showed high dilution linearity (r²>0.99) and precision (< 10% coefficient of variation), low quantification limits (Aβ1–40: 12.5 pg/ml; Aβ1–42: 3.125 pg/ml), and high signal correlation (r²~0.7) with the two-step immunoprecipitation assay. The novel single-step assay showed more efficient recovery of Aβ peptides via fewer immunoprecipitation steps, with significantly higher signal-to-noise ratios, even at plasma sample volumes down to 50 µl. Both assays had equivalent performances in distinguishing non-elevated vs. elevated brain Aβ-PET individuals. The new method enables simplified yet robust evaluation of plasma Aβ biomarkers in Alzheimer’s disease.
Source: Nature Communications
Authors: Yijun Chen, Xuemei Zeng, Marcos Olvera-Rojas, Kelsey R. Sewell, Anuradha Sehrawat, Jeremy Gu, Eva María Triviño-Ibañez, Patricio Solis-Urra, Manuel Gómez- Río, Lauren E. Oberlin, Arthur F. Kramer, Charles H. Hillman, Jeffrey M. Burns, Anna L. Marsland, Chaeryon Kang, Edward McAuley, Milos D. Ikonomovic, Tharick A. Pascoal, Victor L. Villemagne, Oscar L. Lopez, Ann D. Cohen, Irene Esteban-Cornejo, Nathan A. Yates, Kirk I. Erickson, Thomas K. Karikari
Institutions: University of Pittsburgh, University of Pittsburgh Medical Center, Universidad de Granada, Murdoch University, AdventHealth Orlando, AdventHealth, Instituto de Investigación Biosanitaria de Granada, Hospital Universitario Virgen de las Nieves, Universidad Andrés Bello, Weill Cornell Medicine, University of Illinois Urbana-Champaign, Northeastern University, University of Kansas, Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, Instituto de Salud Carlos III, Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, Centro de Investigación Biomédica en Red
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Pittsburgh Foundation, University of Pittsburgh, Ministerio de Ciencia, Innovación y Universidades, National Institutes of Health, European Regional Development Fund, Agencia Estatal de Investigación, National Institute on Aging, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, European Social Fund
Awards: G10563324, G1058046096, G1099014294, G1105844351, G1143115647, G1175115578, G120189231, G1622782223, G2262748287, G2442294994, G2453624921, G2489688429, G2712175038, G278662286, G294895050, G297095765, Roles of Gray Matter Brain Aging and Small Vessel Disease in AD Pathophysiology, G300979063, G3156314389, G3301381536, Myosteatosis, Cognition and Blood Biomarkers of Alzheimer's Disease in Persons of African Ancestry, G3432474565, G34346518, G3480869486, G3583594890, G3726722593, G3880778400, G410571670, G4212894969, G425668148, G451917667, G4544196419, G4873966907, G491712853, G5080475149, G5180908009, G523076202, Subclinical vascular disease and AD pathology in the transition from midlife to old age, G5404395142, G546199279, G5539308778, G5635532810, G589877729, G593054264, G5967599077, G5989133034, G6218905885, G624877701, G6298273575, G641007652, G6420189236, G707218699, G7084143925, G779041648, G7805626310, G7863371703, G8181105605, G8497050386, G8599750628, G8878278103, G8888022036, G9000000726, G9000006693, G9000044512, G9000061071, G9000082041, G9000100763, G9000117497, Frontiers Clinical and Translational Science Institute at the University of Kansas, G9000150905, G9000167399, G9000207975, G9000208814, G9000216768, G9000225582, G9000272169, G9000300274, G9000306279, G9000331231, University of Pittsburgh Clinical and Translational Science Institute, Examining the Persistence of Neurocognitive Benefits of Exercise, Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics, University of Kansas Alzheimer's Disease Research Center (KU ADRC), Mild Cognitive Impairment: A Prospective Community Study, Plasma brain-derived tau: a novel Alzheimer’s disease-type neurodegeneration biomarker with potential to complete the AT(N) scheme in blood, Analytical characterization and validation of blood-biomarkers for monitoring TBI evolution, Predictors of Altered CNS Structure, Function, and Connectomics in the Elderly using a Health Disparities Framework, G929308097
OpenAlex ID: W7125493335