A streamlined, resource-efficient immunoprecipitation-mass spectrometry method for quantifying plasma amyloid-β biomarkers in Alzheimer's disease.
Jonathan M SchottYijun ChenXuemei ZengMarcos Olvera-RojasAnuradha SehrawatTara LaffertyTharick Ali PascoalVictor VillemagnePatricio Solís-UrraEva Triviño-IbañezManuel Gómez-RíAnn CohenMilos IkonomovicIrene Esteban-CornejoKirk EricksonOscar L LopezNathan YatesPublished in: Research square (2024)
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.
Keyphrases
- mass spectrometry
- high throughput
- liquid chromatography
- gas chromatography
- cognitive decline
- high resolution
- high throughput sequencing
- capillary electrophoresis
- high performance liquid chromatography
- computed tomography
- single cell
- air pollution
- magnetic resonance imaging
- multiple sclerosis
- magnetic resonance
- pet ct
- positron emission tomography
- ms ms
- subarachnoid hemorrhage
- liquid chromatography tandem mass spectrometry
- amino acid
- solid phase extraction
- pet imaging