Combining plasma Aβ and p-tau217 improves detection of brain amyloid in non-demented elderly

• DOI: 10.1186/s13195-024-01469-w
• Publication Date: 2024-05-23T00:02:07Z
• Authors: Yoshiki Niimi; Shorena Janelidze; Kenichiro Sato; Naoki Tomita; Tadashi Tsukamoto; Takashi Kato; Kenji Yoshiyama; Hisatomo Kowa; Atsushi Iwata; Ryoko Ihara; Kazushi Suzuki; Kensaku Kasuga; Takeshi Ikeuchi; Kenji Ishii; Kengo Ito; Akinori Nakamura; Michio Senda; Theresa A. Day; Samantha C. Burnham; Leonardo Iaccarino; Michael J. Pontec...; Oskar Hansson; Takeshi Iwatsubo
• Keywords: Male; Neurosciences. Biological psychiatry. Neuropsychiatry; tau Proteins; Cohort Studies; Blood-based biomarker; 03 medical and health sciences; 0302 clinical medicine; Alzheimer Disease; Humans; Amyloid-β; Cognitive Dysfunction; p-tau217; Phosphorylation; RC346-429; Aged; Aged, 80 and over; Amyloid beta-Peptides; Research; Brain; Middle Aged; Peptide Fragments; Cross-Sectional Studies; Positron-Emission Tomography; Female; Neurology. Diseases of the nervous system; Amyloid positron emission tomography; Biomarkers; RC321-571

Abstract 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 early stage Alzheimer’s disease (AD). In this study, we elucidate utility combination plasma amyloid-β (Aβ)-related tau phosphorylated at threonine 217 (p-tau217) predict abnormal Aβ-positron emission tomography (PET) preclinical prodromal AD. Methods We designed cross-sectional study including two ethnically distinct cohorts, Japanese trial-ready cohort preclinica AD (J-TRC) Swedish BioFINDER study. J-TRC included 474 (CDR 0: 331, CDR 0.5: 143). Participants underwent Aβ p-tau217 assessments, Aβ-PET imaging. Findings were replicated 177 participants (cognitively unimpaired: 114, mild cognitive impairment: 63). both Aβ(1-42) (Aβ42) Aβ(1-40) (Aβ40) measured immunoprecipitation-MALDI TOF mass spectrometry (Shimadzu), was with an immunoassay on Meso Scale Discovery platform (Eli Lilly). Results 81 from 71 BioFINDER. Plasma Aβ42/Aβ40 ratio individually showed moderate high accuracies when detecting scans, which improved by combining age, sex APOE genotype models. J-TRC, highest AUCs observed models p-tau217/Aβ42 ratio, , whole (AUC = 0.936), p-tau217, 0 group 0.948), 0.5 0.955), respectively. Each subgroup results BioFINDER, where seen Aβ42/40 cognitively unimpaired 0.938), impairment 0.914). Conclusions Combination Aβ-related exhibits performance predicting positivity. Adding basic information (i.e., sex, ε genotype) prediction AD, but not could be highly useful pre-screening