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Performance of the plasma Aβ42/Aβ40 ratio, measured with a novel HPLC-MS/MS method, as a biomarker of amyloid PET status in a DPUK-KOREAN cohort.

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  • Additional Information
    • Corporate Authors:
    • Source:
      Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 101511643 Publication Model: Electronic Cited Medium: Internet ISSN: 1758-9193 (Electronic) NLM ISO Abbreviation: Alzheimers Res Ther Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : BioMed Central Ltd.
    • Subject Terms:
    • Abstract:
      Background: We assessed the feasibility of plasma Aβ42/Aβ40 determined using a novel liquid chromatography-mass spectrometry method (LC-MS) as a useful biomarker of PET status in a Korean cohort from the DPUK Study.
      Methods: A total of 580 participants belonging to six groups, Alzheimer's disease dementia (ADD, n = 134), amnestic mild cognitive impairment (aMCI, n = 212), old controls (OC, n = 149), young controls (YC, n = 15), subcortical vascular cognitive impairment (SVCI, n = 58), and cerebral amyloid angiopathy (CAA, n = 12), were included in this study. Plasma Aβ40 and Aβ42 were quantitated using a new antibody-free, LC-MS, which drastically reduced the sample preparation time and cost. We performed receiver operating characteristic (ROC) analysis to develop the cutoff of Aβ42/Aβ40 and investigated its performance predicting centiloid-based PET positivity (PET+).
      Results: Plasma Aβ42/Aβ40 were lower for PET+ individuals in ADD, aMCI, OC, and SVCI (p < 0.001), but not in CAA (p = 0.133). In the group of YC, OC, aMCI, and ADD groups, plasma Aβ42/Aβ40 predicted PET+ with an area under the ROC curve (AUC) of 0.814 at a cutoff of 0.2576. When adding age, APOE4, and diagnosis, the AUC significantly improved to 0.912.
      Conclusion: Plasma Aβ42/Aβ40, as measured by this novel LC-MS method, showed good discriminating performance based on PET positivity.
      (© 2021. The Author(s).)
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    • Grant Information:
      MR/L023784/2 United Kingdom MRC_ Medical Research Council; MR/T033371/1 United Kingdom MRC_ Medical Research Council; MR/L023784/2 United Kingdom MRF_ MRF_
    • Contributed Indexing:
      Keywords: Alzheimer’s disease; Amyloid; Aβ42/Aβ40; Biomarker; Liquid chromatography-mass spectrometry; Plasma
    • Accession Number:
      0 (Amyloid beta-Peptides)
      0 (Biomarkers)
      0 (Peptide Fragments)
      0 (amyloid beta-protein (1-42))
    • Publication Date:
      Date Created: 20211023 Date Completed: 20211028 Latest Revision: 20250530
    • Publication Date:
      20250530
    • Accession Number:
      PMC8540152
    • Accession Number:
      10.1186/s13195-021-00911-7
    • Accession Number:
      34686209