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

• Published in: Alzheimer's research & therapy 2024-05, Vol.16 (1), p.115-12, Article 115
• Main Authors: Niimi, Yoshiki, Janelidze, Shorena, Sato, Kenichiro, Tomita, Naoki, Tsukamoto, Tadashi, Kato, Takashi, Yoshiyama, Kenji, Kowa, Hisatomo, Iwata, Atsushi, Ihara, Ryoko, Suzuki, Kazushi, Kasuga, Kensaku, Ikeuchi, Takeshi, Ishii, Kenji, Ito, Kengo, Nakamura, Akinori, Senda, Michio, Day, Theresa A, Burnham, Samantha C, Iaccarino, Leonardo, Pontecorvo, Michael J, Hansson, Oskar, Iwatsubo, Takeshi
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - diagnosis; Alzheimer Disease - diagnostic imaging; Amyloid beta-Peptides - blood; Amyloid beta-Peptides - metabolism; Amyloid positron emission tomography; Amyloid-β; Biomarkers - blood; Blood-based biomarker; Brain - diagnostic imaging; Brain - metabolism; Clinical Medicine; Cognitive Dysfunction - blood; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - diagnostic imaging; Cohort Studies; Cross-Sectional Studies; Female; Humans; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Middle Aged; Neurologi; Neurology; p-tau217; Peptide Fragments - blood; Phosphorylation; Positron-Emission Tomography - methods; tau Proteins - blood
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-024-01469-w

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-β (Aβ)-related biomarkers and tau phosphorylated at threonine 217 (p-tau217) to predict abnormal Aβ-positron emission tomography (PET) in the preclinical and prodromal AD. 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 Aβ and p-tau217 assessments, and Aβ-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 Aβ(1-42) (Aβ42) and Aβ(1-40) (Aβ40) 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). Aβ-PET was abnormal in 81 participants from J-TRC and 71 participants from BioFINDER. Plasma Aβ42/Aβ40 ratio and p-tau217 individually showed moderate to high accuracies when detecting abnormal Aβ-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/Aβ42 ratio, APOE, age, sex in the whole cohort (AUC = 0.936), combining p-tau217, Aβ42/Aβ40 ratio, APOE, age, sex in the CDR 0 group (AUC = 0.948), and combining p-tau217/Aβ42 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, Aβ42/40 ratio, APOE, age, sex in cognitively unimpaired (AUC = 0.938), and p-tau217/Aβ42 ratio, APOE, age, sex in mild cognitive impairment (AUC = 0.914). Combination of plasma Aβ-related biomarkers and p-tau217 exhibits high performance when predicting Aβ-PET positivity. Adding basic clinical information (i.e., age, sex, APOE ε genotype) improved the prediction in preclinical AD, but not in prodromal AD. Combination of Aβ-related biomarkers and p-tau217 could be highly useful for pre-screening of participants in clinical trials o