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

Alzheimer’s Research & Therapy

on behalf of DPUK¹  Pedro Pesini²  Leticia Sarasa²  José Antonio Allué²  Sergio Castillo²  Ji Sun Kim³  Hyemin Jang³  Hee Jin Kim³  Hye Joo Lee³  Sang Won Seo³  Duk L. Na³  Chi-Hun Kim⁴  John Gallacher⁵ 

[1] ;Araclon Biotech-Grifols;Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine;Department of Neurology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital;Department of Psychiatry, University of Oxford, Warneford Hospital;

关键词: Biomarker;    Alzheimer’s disease;    Amyloid;    Plasma;    Aβ42/Aβ40;    Liquid chromatography-mass spectrometry;   

DOI  :  10.1186/s13195-021-00911-7

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown