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

<p><strong>Background:</strong> 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.</p> <p><strong>Methods:<...

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Main Authors: Jang, H, Kim, C-H, Seo, SW, Na, D, Gallagher, J
Format: Journal article
Language:English
Published: BioMed Central 2021
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author Jang, H
Kim, C-H
Seo, SW
Na, D
Gallagher, J
Seo, SW
author_facet Jang, H
Kim, C-H
Seo, SW
Na, D
Gallagher, J
Seo, SW
author_sort Jang, H
collection OXFORD
description <p><strong>Background:</strong> 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.</p> <p><strong>Methods:</strong> 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, HPLC-MS/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 (CL)-based PET positivity (PET+).</p> <p><strong>Results:</strong> Aβ42/Aβ40 ratios were lower for PET positive individuals in the ADD, aMCI, OC, and SVCI (p<0.001) groups, but not in CAA group (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.</p> <p><strong>Conclusion:</strong> Plasma Aβ42/Aβ40 ratio, as measured by this novel LC-MS method, showed good discriminating performance based on PET positivity.</p>
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spelling oxford-uuid:46725f62-14ea-4dfe-94c6-eddfdd6d91ee2022-03-26T15:13:46ZPerformance of plasma Aβ42/Aβ40 ratio, measured with a novel HPLC-MS/MS method, as a biomarker of amyloid-PET status in a DPUK-KOREAN cohortJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:46725f62-14ea-4dfe-94c6-eddfdd6d91eeEnglishSymplectic ElementsBioMed Central2021Jang, HKim, C-HSeo, SWNa, DGallagher, JSeo, SW<p><strong>Background:</strong> 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.</p> <p><strong>Methods:</strong> 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, HPLC-MS/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 (CL)-based PET positivity (PET+).</p> <p><strong>Results:</strong> Aβ42/Aβ40 ratios were lower for PET positive individuals in the ADD, aMCI, OC, and SVCI (p<0.001) groups, but not in CAA group (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.</p> <p><strong>Conclusion:</strong> Plasma Aβ42/Aβ40 ratio, as measured by this novel LC-MS method, showed good discriminating performance based on PET positivity.</p>
spellingShingle Jang, H
Kim, C-H
Seo, SW
Na, D
Gallagher, J
Seo, SW
Performance of plasma Aβ42/Aβ40 ratio, measured with a novel HPLC-MS/MS method, as a biomarker of amyloid-PET status in a DPUK-KOREAN cohort
title Performance of plasma Aβ42/Aβ40 ratio, measured with a novel HPLC-MS/MS method, as a biomarker of amyloid-PET status in a DPUK-KOREAN cohort
title_full Performance of plasma Aβ42/Aβ40 ratio, measured with a novel HPLC-MS/MS method, as a biomarker of amyloid-PET status in a DPUK-KOREAN cohort
title_fullStr Performance of plasma Aβ42/Aβ40 ratio, measured with a novel HPLC-MS/MS method, as a biomarker of amyloid-PET status in a DPUK-KOREAN cohort
title_full_unstemmed Performance of plasma Aβ42/Aβ40 ratio, measured with a novel HPLC-MS/MS method, as a biomarker of amyloid-PET status in a DPUK-KOREAN cohort
title_short Performance of plasma Aβ42/Aβ40 ratio, measured with a novel HPLC-MS/MS method, as a biomarker of amyloid-PET status in a DPUK-KOREAN cohort
title_sort performance of 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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