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  • Palmqvist, SebastianLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital (författare)

Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders

  • Artikel/kapitelEngelska2020

Förlag, utgivningsår, omfång ...

  • American Medical Association (AMA),2020

Nummerbeteckningar

  • LIBRIS-ID:oai:gup.ub.gu.se/297147
  • https://gup.ub.gu.se/publication/297147URI
  • https://doi.org/10.1001/jama.2020.12134DOI
  • https://lup.lub.lu.se/record/d2db2ecc-52e4-4a6f-adff-0149b1e06854URI

Kompletterande språkuppgifter

  • Språk:engelska

Ingår i deldatabas

Klassifikation

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

Anmärkningar

  • Key PointsQuestionWhat is the discriminative accuracy of plasma phospho-tau217 (P-tau217) for differentiating Alzheimer disease from other neurodegenerative disorders? FindingsIn this cross-sectional study that included 1402 participants from 3 selected cohorts, plasma P-tau217 discriminated Alzheimer disease from other neurodegenerative diseases (area under the receiver operating characteristic curve of 0.89 in a neuropathologically defined cohort and 0.96 in a clinically defined cohort), with performance that was significantly better than established Alzheimer disease plasma- and MRI-based biomarkers but not significantly different from key CSF- or PET-based biomarkers. MeaningAlthough plasma P-tau217 was able to discriminate Alzheimer disease from other neurodegenerative diseases, further research is needed to validate the findings in unselected and diverse populations, optimize the assay, and determine its potential role in clinical care. ImportanceThere are limitations in current diagnostic testing approaches for Alzheimer disease (AD). ObjectiveTo examine plasma tau phosphorylated at threonine 217 (P-tau217) as a diagnostic biomarker for AD. Design, Setting, and ParticipantsThree cross-sectional cohorts: an Arizona-based neuropathology cohort (cohort 1), including 34 participants with AD and 47 without AD (dates of enrollment, May 2007-January 2019); the Swedish BioFINDER-2 cohort (cohort 2), including cognitively unimpaired participants (n=301) and clinically diagnosed patients with mild cognitive impairment (MCI) (n=178), AD dementia (n=121), and other neurodegenerative diseases (n=99) (April 2017-September 2019); and a Colombian autosomal-dominant AD kindred (cohort 3), including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers (December 2013-February 2017). ExposuresPlasma P-tau217. Main Outcomes and MeasuresPrimary outcome was the discriminative accuracy of plasma P-tau217 for AD (clinical or neuropathological diagnosis). Secondary outcome was the association with tau pathology (determined using neuropathology or positron emission tomography [PET]). ResultsMean age was 83.5 (SD, 8.5) years in cohort 1, 69.1 (SD, 10.3) years in cohort 2, and 35.8 (SD, 10.7) years in cohort 3; 38% were women in cohort 1, 51% in cohort 2, and 57% in cohort 3. In cohort 1, antemortem plasma P-tau217 differentiated neuropathologically defined AD from non-AD (area under the curve [AUC], 0.89 [95% CI, 0.81-0.97]) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P<.05). The discriminative accuracy of plasma P-tau217 in cohort 2 for clinical AD dementia vs other neurodegenerative diseases (AUC, 0.96 [95% CI, 0.93-0.98]) was significantly higher than plasma P-tau181, plasma NfL, and MRI measures (AUC range, 0.50-0.81; P<.001) but not significantly different compared with cerebrospinal fluid (CSF) P-tau217, CSF P-tau181, and tau-PET (AUC range, 0.90-0.99; P>.15). In cohort 3, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers, compared with noncarriers, from approximately 25 years and older, which is 20 years prior to estimated onset of MCI among mutation carriers. Plasma P-tau217 levels correlated with tau tangles in participants with (Spearman rho =0.64; P<.001), but not without (Spearman =0.15; P=.33), beta -amyloid plaques in cohort 1. In cohort 2, plasma P-tau217 discriminated abnormal vs normal tau-PET scans (AUC, 0.93 [95% CI, 0.91-0.96]) with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF A beta 42:A beta 40 ratio, and MRI measures (AUC range, 0.67-0.90; P<.05), but its performance was not significantly different compared with CSF P-tau217 (AUC, 0.96; P=.22). Conclusions and RelevanceAmong 1402 participants from 3 selected cohorts, plasma P-tau217 discriminated AD from other neurodegenerative diseases, with significantly higher accuracy than established plasma- and MRI-based biomarkers, and its performance was not significantly different from key CSF- or PET-based measures. Further research is needed to optimize the assay, validate the findings in unselected and diverse populations, and determine its potential role in clinical care. This cross-sectional study compares the accuracy of plasma tau phosphorylated at threonine 217 (P-tau217) levels vs other plasma-, MRI-, CSF-, and PET-based markers for distinguishing Alzheimer from other neurodegenerative diseases in 3 cohorts in Arizona, Sweden, and Columbia with or at risk for dementia.

Ämnesord och genrebeteckningar

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

  • Janelidze, ShorenaLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)nkir-sje (författare)
  • Quiroz, Y. T.University of Antioquia,Massachusetts General Hospital,Harvard University (författare)
  • Zetterberg, Henrik,1973University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Sahlgrenska University Hospital,University College London(Swepub:lu)med-hiz (författare)
  • Lopera, F.University of Antioquia (författare)
  • Stomrud, ErikLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-esr (författare)
  • Su, Y.Banner Alzheimer's Institute (författare)
  • Chen, Y. H.Banner Alzheimer's Institute (författare)
  • Serrano, G. E.Banner Sun Health Research Institute (författare)
  • Leuzy, AntoineLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)an3415le (författare)
  • Mattsson-Carlgren, NiklasLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Clinical Memory Research,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,Skåne University Hospital(Swepub:lu)med-nmn (författare)
  • Strandberg, OlofLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)teor-osn (författare)
  • Smith, RubenLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-rsm (författare)
  • Villegas, A.University of Antioquia (författare)
  • Sepulveda-Falla, D.University of Antioquia,University Medical Center Hamburg-Eppendorf (författare)
  • Chai, X. Y.Eli Lilly and Company (författare)
  • Proctor, N. K.Eli Lilly and Company (författare)
  • Beach, T. G.Banner Sun Health Research Institute (författare)
  • Blennow, Kaj,1958University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Sahlgrenska University Hospital(Swepub:lu)med-kbw (författare)
  • Dage, J. L.Eli Lilly and Company (författare)
  • Reiman, E. M.Arizona State University,Banner Alzheimer's Institute,University of Arizona (författare)
  • Hansson, OskarLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-ohn (författare)
  • Klinisk minnesforskningForskargrupper vid Lunds universitet (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Jama-Journal of the American Medical Association: American Medical Association (AMA)324:8, s. 772-7810098-7484

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