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Sökning: onr:"swepub:oai:lup.lub.lu.se:1a5bad38-6c34-4c00-934a-41043a446d39" > Combining plasma Aβ...

  • Niimi, YoshikiUniversity of Tokyo Hospital (författare)

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

  • Artikel/kapitelEngelska2024

Förlag, utgivningsår, omfång ...

  • 2024

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:1a5bad38-6c34-4c00-934a-41043a446d39
  • https://lup.lub.lu.se/record/1a5bad38-6c34-4c00-934a-41043a446d39URI
  • https://doi.org/10.1186/s13195-024-01469-wDOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • 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.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Janelidze, ShorenaLund 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(Swepub:lu)nkir-sje (författare)
  • Sato, KenichiroGraduate School of Medicine, University of Tokyo,University of Tokyo Hospital (författare)
  • Tomita, NaokiTohoku University (författare)
  • Tsukamoto, Tadashi (författare)
  • Kato, TakashiNational Center for Geriatrics and Gerontology (författare)
  • Yoshiyama, KenjiOsaka University (författare)
  • Kowa, HisatomoKobe university (författare)
  • Iwata, Atsushi (författare)
  • Ihara, Ryoko (författare)
  • Suzuki, KazushiNational Defense Medical College (författare)
  • Kasuga, Kensaku (författare)
  • Ikeuchi, Takeshi (författare)
  • Ishii, Kenji (författare)
  • Ito, KengoNational Center for Geriatrics and Gerontology (författare)
  • Nakamura, AkinoriNational Center for Geriatrics and Gerontology (författare)
  • Senda, Michio (författare)
  • Day, Theresa A.Eli Lilly and Company (författare)
  • Burnham, Samantha C.Eli Lilly and Company (författare)
  • Iaccarino, LeonardoEli Lilly and Company (författare)
  • Pontecorvo, Michael J.Eli Lilly and Company (författare)
  • Hansson, OskarLund 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(Swepub:lu)mphy-ohn (författare)
  • Iwatsubo, TakeshiGraduate School of Medicine, University of Tokyo,University of Tokyo Hospital (författare)
  • University of Tokyo HospitalKlinisk minnesforskning (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Alzheimer's Research and Therapy16:11758-9193

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