Combining plasma Aβ and p-tau217 improves detection of brain amyloid in non-demented elderly
(2024) In Alzheimer's Research and Therapy 16(1).- 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 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:... (More)
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.
(Less)
- author
- Niimi, Yoshiki
; Janelidze, Shorena
LU
; 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
LU
and Iwatsubo, Takeshi
(Less) - organization
- publishing date
- 2024-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Amyloid positron emission tomography, Amyloid-β, Blood-based biomarker, p-tau217
- in
- Alzheimer's Research and Therapy
- volume
- 16
- issue
- 1
- article number
- 115
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85194050788
- pmid:38778353
- ISSN
- 1758-9193
- DOI
- 10.1186/s13195-024-01469-w
- language
- English
- LU publication?
- yes
- id
- 1a5bad38-6c34-4c00-934a-41043a446d39
- date added to LUP
- 2024-06-04 14:25:48
- date last changed
- 2024-06-18 15:09:44
@article{1a5bad38-6c34-4c00-934a-41043a446d39,
abstract = {{<p>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.</p>}},
author = {{Niimi, Yoshiki and Janelidze, Shorena and Sato, Kenichiro and Tomita, Naoki and Tsukamoto, Tadashi and Kato, Takashi and Yoshiyama, Kenji and Kowa, Hisatomo and Iwata, Atsushi and Ihara, Ryoko and Suzuki, Kazushi and Kasuga, Kensaku and Ikeuchi, Takeshi and Ishii, Kenji and Ito, Kengo and Nakamura, Akinori and Senda, Michio and Day, Theresa A. and Burnham, Samantha C. and Iaccarino, Leonardo and Pontecorvo, Michael J. and Hansson, Oskar and Iwatsubo, Takeshi}},
issn = {{1758-9193}},
keywords = {{Amyloid positron emission tomography; Amyloid-β; Blood-based biomarker; p-tau217}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Alzheimer's Research and Therapy}},
title = {{Combining plasma Aβ and p-tau217 improves detection of brain amyloid in non-demented elderly}},
url = {{http://dx.doi.org/10.1186/s13195-024-01469-w}},
doi = {{10.1186/s13195-024-01469-w}},
volume = {{16}},
year = {{2024}},
}