Combining plasma Aβ and p-tau217 improves detection of brain amyloid in non-demented elderly.
In: Alzheimer's research & therapy, Jg. 16 (2024-05-23), Heft 1, S. 115
Online
academicJournal
Zugriff:
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-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.
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 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).
Results: 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).
Conclusions: 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.
(© 2024. The Author(s).)
Titel: |
Combining plasma Aβ and p-tau217 improves detection of brain amyloid in non-demented elderly.
|
---|---|
Autor/in / Beteiligte Person: | 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 |
Link: | |
Zeitschrift: | Alzheimer's research & therapy, Jg. 16 (2024-05-23), Heft 1, S. 115 |
Veröffentlichung: | [London] : BioMed Central Ltd., 2024 |
Medientyp: | academicJournal |
ISSN: | 1758-9193 (electronic) |
DOI: | 10.1186/s13195-024-01469-w |
Schlagwort: |
|
Sonstiges: |
|