부산대학교 도서관

Background Maximizing the efficiency to screen amyloid-positive individuals in asymptomatic and non-demented aged population using blood-based biomarkers is essential for future success of clinical trials in the early stage of Alzheimer's disease (AD). In this study, we elucidate the utility of combination of plasma amyloid-[beta] (A[beta])-related biomarkers and tau phosphorylated at threonine 217 (p-tau217) to predict abnormal A[beta]-positron emission tomography (PET) in the preclinical and prodromal AD. Methods We designed the cross-sectional study including two ethnically distinct cohorts, the Japanese trial-ready cohort for preclinica and prodromal AD (J-TRC) and the Swedish BioFINDER study. J-TRC included 474 non-demented individuals (CDR 0: 331, CDR 0.5: 143). Participants underwent plasma A[beta] and p-tau217 assessments, and A[beta]-PET imaging. Findings in J-TRC were replicated in the BioFINDER cohort including 177 participants (cognitively unimpaired: 114, mild cognitive impairment: 63). In both cohorts, plasma A[beta](1-42) (A[beta]42) and A[beta](1-40) (A[beta]40) were measured using immunoprecipitation-MALDI TOF mass spectrometry (Shimadzu), and p-tau217 was measured with an immunoassay on the Meso Scale Discovery platform (Eli Lilly). Results A[beta]-PET was abnormal in 81 participants from J-TRC and 71 participants from BioFINDER. Plasma A[beta]42/A[beta]40 ratio and p-tau217 individually showed moderate to high accuracies when detecting abnormal A[beta]-PET scans, which were improved by combining plasma biomarkers and by including age, sex and APOE genotype in the models. In J-TRC, the highest AUCs were observed for the models combining p-tau217/A[beta]42 ratio, APOE, age, sex in the whole cohort (AUC = 0.936), combining p-tau217, A[beta]42/A[beta]40 ratio, APOE, age, sex in the CDR 0 group (AUC = 0.948), and combining p-tau217/A[beta]42 ratio, APOE, age, sex in the CDR 0.5 group (AUC = 0.955), respectively. Each subgroup results were replicated in BioFINDER, where the highest AUCs were seen for models combining p-tau217, A[beta]42/40 ratio, APOE, age, sex in cognitively unimpaired (AUC = 0.938), and p-tau217/A[beta]42 ratio, APOE, age, sex in mild cognitive impairment (AUC = 0.914). Conclusions Combination of plasma A[beta]-related biomarkers and p-tau217 exhibits high performance when predicting A[beta]-PET positivity. Adding basic clinical information (i.e., age, sex, APOE [epsilon] genotype) improved the prediction in preclinical AD, but not in prodromal AD. Combination of A[beta]-related biomarkers and p-tau217 could be highly useful for pre-screening of participants in clinical trials of preclinical and prodromal AD. Keywords: Blood-based biomarker, p-tau217, Amyloid-[beta], Amyloid positron emission tomography
Author(s): Yoshiki Niimi[sup.1] , Shorena Janelidze[sup.2] , Kenichiro Sato[sup.1,3] , Naoki Tomita[sup.4,5] , Tadashi Tsukamoto[sup.6] , Takashi Kato[sup.7] , Kenji Yoshiyama[sup.8] , Hisatomo Kowa[sup.9] , Atsushi Iwata[sup.10] , Ryoko Ihara[sup.10] [...]