The AIBL was used as the discovery cohort in the study. The AIBL study is a longitudinal study of aging, neuroimaging, biomarkers, lifestyle, and clinical and neuropsychological analysis, with a focus on early detection and lifestyle intervention (www.aibl.csiro.au). Specifics regarding participant recruitment, study design, and clinical assessments were previously described (35). Plasma samples from 190 AIBL participants with baseline Aβ PET imaging (11C-PiB) were selected, with a focus on individuals without cognitive deficits at baseline. Further details about the 11C-PiB imaging protocols for the AIBL cohort were previously described (36). Participants were categorized as Aβ− and Aβ+ based on the 11C-PiB SUVR cutoff of 1.4 (37). For plasma preparation, whole blood (80 ml) was collected in the morning (overnight fasting) by venepuncture and centrifuged at 200g (20°C) for 10 min. The platelet-rich plasma was further spun at 800g (20°C) for 15 min (9). The KARVIAH was used as an independent replication cohort in this study. Participants recruited to this cohort were residents of Anglicare (Sydney, NSW, Australia), and all volunteers were required to meet the set screening inclusion and exclusion criteria to be eligible for the KARVIAH cohort (38). Selection of 94 KARVIAH participants was dependent on the availability of 18FBB images for each subject, where an Aβ SUVR cutoff score of 1.35 was used to categorize Aβ− and Aβ+ (39). All KARVIAH participants were cognitively unimpaired based on their Mini Mental State Examination score of >26. Plasma preparation for 94 KARVIAH participants followed the same protocol as AIBL participants.

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