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Combining plasma Aβ...
Combining plasma Aβ and p-tau217 improves detection of brain amyloid in non-demented elderly
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- Niimi, Yoshiki (author)
- University of Tokyo Hospital
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- Janelidze, Shorena (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas
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- Sato, Kenichiro (author)
- Graduate School of Medicine, University of Tokyo,University of Tokyo Hospital
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- Tomita, Naoki (author)
- Tohoku University
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Tsukamoto, Tadashi (author)
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- Kato, Takashi (author)
- National Center for Geriatrics and Gerontology
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- Yoshiyama, Kenji (author)
- Osaka University
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- Kowa, Hisatomo (author)
- Kobe university
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Iwata, Atsushi (author)
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Ihara, Ryoko (author)
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- Suzuki, Kazushi (author)
- National Defense Medical College
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Kasuga, Kensaku (author)
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Ikeuchi, Takeshi (author)
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Ishii, Kenji (author)
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- Ito, Kengo (author)
- National Center for Geriatrics and Gerontology
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- Nakamura, Akinori (author)
- National Center for Geriatrics and Gerontology
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Senda, Michio (author)
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- Day, Theresa A. (author)
- Eli Lilly and Company
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- Burnham, Samantha C. (author)
- Eli Lilly and Company
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- Iaccarino, Leonardo (author)
- Eli Lilly and Company
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- Pontecorvo, Michael J. (author)
- Eli Lilly and Company
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- Hansson, Oskar (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital,University of Tokyo Hospital
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- Iwatsubo, Takeshi (author)
- University of Tokyo Hospital,Graduate School of Medicine, University of Tokyo
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: Alzheimer's Research and Therapy. - 1758-9193. ; 16:1
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http://dx.doi.org/10... (free)
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- Amyloid positron emission tomography
- Amyloid-β
- Blood-based biomarker
- p-tau217
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Niimi, Yoshiki
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Janelidze, Shore ...
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Sato, Kenichiro
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Tomita, Naoki
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Tsukamoto, Tadas ...
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Kato, Takashi
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show more...
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Yoshiyama, Kenji
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Kowa, Hisatomo
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Iwata, Atsushi
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Ihara, Ryoko
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Suzuki, Kazushi
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Kasuga, Kensaku
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Ikeuchi, Takeshi
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Ishii, Kenji
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Ito, Kengo
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Nakamura, Akinor ...
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Senda, Michio
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Day, Theresa A.
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Burnham, Samanth ...
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Iaccarino, Leona ...
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Pontecorvo, Mich ...
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Hansson, Oskar
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Iwatsubo, Takesh ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
- Articles in the publication
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Alzheimer's Rese ...
- By the university
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Lund University