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

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 of preclinical and prodromal AD.

Niimi Y ，Janelidze S ，Sato K ，Tomita N ，Tsukamoto T ，Kato T ，Yoshiyama K ，Kowa H ，Iwata A ，Ihara R ，Suzuki K ，Kasuga K ，Ikeuchi T ，Ishii K ，Ito K ，Nakamura A ，Senda M ，Day TA ，Burnham SC ，Iaccarino L ，Pontecorvo MJ ，Hansson O ，Iwatsubo T ... -  《Alzheimers Research & Therapy》

Plasma Phosphorylated Tau 217 and Aβ42/40 to Predict Early Brain Aβ Accumulation in People Without Cognitive Impairment.

Janelidze S ，Barthélemy NR ，Salvadó G ，Schindler SE ，Palmqvist S ，Mattsson-Carlgren N ，Braunstein JB ，Ovod V ，Bollinger JG ，He Y ，Li Y ，Raji CA ，Morris JC ，Holtzman DM ，Ashton NJ ，Blennow K ，Stomrud E ，Bateman RJ ，Hansson O ... -  《-》

Biomarker-Based Prediction of Longitudinal Tau Positron Emission Tomography in Alzheimer Disease.

Leuzy A ，Smith R ，Cullen NC ，Strandberg O ，Vogel JW ，Binette AP ，Borroni E ，Janelidze S ，Ohlsson T ，Jögi J ，Ossenkoppele R ，Palmqvist S ，Mattsson-Carlgren N ，Klein G ，Stomrud E ，Hansson O ... -  《-》

Amyloid and Tau Prediction of Cognitive and Functional Decline in Unimpaired Older Individuals: Longitudinal Data from the A4 and LEARN Studies.

Sperling RA ，Donohue MC ，Rissman RA ，Johnson KA ，Rentz DM ，Grill JD ，Heidebrink JL ，Jenkins C ，Jimenez-Maggiora G ，Langford O ，Liu A ，Raman R ，Yaari R ，Holdridge KC ，Sims JR ，Aisen PS ... -  《-》

Associations of Plasma Phospho-Tau217 Levels With Tau Positron Emission Tomography in Early Alzheimer Disease.

Janelidze S ，Berron D ，Smith R ，Strandberg O ，Proctor NK ，Dage JL ，Stomrud E ，Palmqvist S ，Mattsson-Carlgren N ，Hansson O ... -  《-》