| Summary: | <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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