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Targeted blood proteome profiling using NULISAseq identifies a high-performance biomarker panel for Aβ pathology

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This study developed a novel blood test to quantify amyloid beta plaque deposition in Alzheimer's disease (AD). The assay accurately measures amyloid pathology, aiding early AD screening and monitoring.

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Area of Science:

  • Neurodegenerative disease research
  • Biomarker discovery
  • Proteomics

Background:

  • Current Alzheimer's disease (AD) blood biomarkers detect amyloid beta (Aβ) presence but cannot quantify plaque load.
  • Accurate quantification of Aβ pathology is crucial for early diagnosis and disease monitoring.

Purpose of the Study:

  • To develop a blood-based biomarker panel for quantifying Aβ plaque deposition in Alzheimer's disease.
  • To analyze proteomic changes associated with Aβ pathology progression.

Main Methods:

  • Plasma proteins (325) were profiled using the NULISAseq platform in a Hong Kong Chinese cohort.
  • Machine learning was employed to identify and construct a biomarker panel for Aβ quantification.
  • Aβ pathology progression was analyzed by examining blood proteome dysregulation trajectories.

Main Results:

  • 43 blood proteins correlated with Aβ plaque accumulation were identified.
  • An 8-protein biomarker panel demonstrated strong correlation with amyloid PET Centiloid values (r=0.89).
  • The panel accurately quantified Aβ deposition and classified early-stage AD pathology (AUC=0.93).

Conclusions:

  • A systematic profile of dynamic protein alterations during Aβ pathology progression was established.
  • A novel biomarker assay was developed for accurate quantification of Aβ pathology.
  • This assay shows potential for early Alzheimer's disease screening and monitoring of amyloid pathology.