Abstract
BackgroundWe 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.MethodsA 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+).ResultsPlasma 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.ConclusionPlasma Aβ42/Aβ40, as measured by this novel LC-MS method, showed good discriminating performance based on PET positivity.
Highlights
Alzheimer’s disease (AD) is characterized by amyloid β (Aβ) deposition in the brain
Considering that Aβ kinetics in the plasma Aβ level changes as the disease progresses [5], the association of plasma Aβ and Aβ deposition in the brain might vary depending on the three cognitive stages: normal control, mild cognitive impairment (MCI), and dementia
We can assume that age, APOE genotype, and the cognitive stage might affect the relationship between the plasma Aβ level and Aβ deposition detected on Positron emission tomography (PET)
Summary
Alzheimer’s disease (AD) is characterized by amyloid β (Aβ) deposition in the brain. Due to the rapid development of Aβ biomarker testing, earlier diagnosis of AD has become possible. Changes in Aβ fluid biomarkers may occur earlier than Aβ PET in the preclinical phase of the AD continuum [17, 18], as it is known that the dysregulated kinetics of soluble Aβ precedes Aβ deposition in the brain [19]. Considering that Aβ kinetics in the plasma Aβ level changes as the disease progresses [5], the association of plasma Aβ and Aβ deposition in the brain might vary depending on the three cognitive stages: normal control, mild cognitive impairment (MCI), and dementia. We can assume that age, APOE genotype, and the cognitive stage might affect the relationship between the plasma Aβ level and Aβ deposition detected on PET. We assessed the feasibility of plasma Aβ42/Aβ40 determined using a novel liquid chromatographymass spectrometry method (LC-MS) as a useful biomarker of PET status in a Korean cohort from the DPUK Study
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