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  • Janelidze, ShorenaLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups (författare)

Head-to-head comparison of 10 plasma phospho-tau assays in prodromal Alzheimer's disease.

  • Artikel/kapitelEngelska2023

Förlag, utgivningsår, omfång ...

  • 2022-09-10
  • Oxford University Press (OUP),2023

Nummerbeteckningar

  • LIBRIS-ID:oai:gup.ub.gu.se/322011
  • https://gup.ub.gu.se/publication/322011URI
  • https://doi.org/10.1093/brain/awac333DOI
  • https://lup.lub.lu.se/record/7bbed2de-283c-4289-b8cd-7d53ad457aeaURI

Kompletterande språkuppgifter

  • Språk:engelska

Ingår i deldatabas

Klassifikation

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

Anmärkningar

  • Plasma phospho-tau (p-tau) species have emerged as the most promising blood-based biomarkers of Alzheimer's disease. Here, we performed a head-to-head comparison of p-tau181, p-tau217 and p-tau231 measured using 10 assays to detect abnormal brain amyloid-β status and predict future progression to Alzheimer's dementia. The study included 135 patients with baseline diagnosis of mild cognitive impairment (mean age 72.4 years; 60.7% women) who were followed for an average of 4.9 years. Seventy-one participants had abnormal Aβ-status (i.e., abnormal CSF Aβ42/40) at baseline; and 45 of these Aβ-positive participants progressed to Alzheimer's dementia during follow-up. P-tau concentrations were determined in baseline plasma and CSF. P-tau217 and p-tau181 were both measured using immunoassays developed by Lilly Research Laboratories (Lilly) and mass spectrometry assays developed at Washington University (WashU). P-tau217 was also analysed using Simoa immunoassay developed by Janssen Research and Development (Janss). P-tau181 was measured using Simoa immunoassay from ADxNeurosciences (ADx), Lumipulse immunoassay from Fujirebio (Fuji) and Splex immunoassay from Mesoscale Discovery (Splex). Both p-tau181 and p-tau231 were quantified using Simoa immunoassay developed at the University of Gothenburg (UGOT). We found that the mass spectrometry-based p-tau217 (p-tau217WashU) exhibited significantly better performance than all other plasma p-tau biomarkers when detecting abnormal Aβ status (AUC=0.947; pdiff<0.015) or progression to Alzheimer's dementia (AUC=0.932; pdiff<0.027). Among immunoassays, p-tau217Lilly had the highest AUCs (0.886-0.889), which was not significantly different from the AUCs of p-tau217Janss, p-tau181ADx and p-tau181WashU (AUCrange, 0.835-0.872; pdiff>0.09), but higher compared with AUC of p-tau231UGOT, p-tau181Lilly, p-tau181UGOT, p-tau181Fuji, and p-tau181Splex (AUCrange, 0.642-0.813; pdiff ≤0.029). Correlations between plasma and CSF values were strongest for p-tau217WashU (R=0.891) followed by p-tau217Lilly (R=0.755; pdiff=0.003 vs p-tau217WashU) and weak to moderate for the rest of the p-tau biomarkers (Rrange, 0.320-0.669). In conclusion, the findings suggest that among all tested plasma p-tau assays, mass spectrometry-based measures of p-tau217 perform best when identifying mild cognitive impairment patients with abnormal brain Aβ or those who will subsequently progress to Alzheimer's dementia. Several other assays (p-tau217Lilly, p-tau217Janss, p-tau181ADx, and p-tau181WashU) showed relatively high and consistent accuracy across both outcomes. The results further indicate that the highest performing assays have performance metrics that rival the gold standards of Aβ-PET and CSF. If further validated, our findings will have significant impacts in diagnosis, screening and treatment for Alzheimer's dementia in the future.

Ämnesord och genrebeteckningar

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

  • Bali, DivyaLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)di3408ba (författare)
  • Ashton, Nicholas J.Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,King's College London(Swepub:gu)xashtn (författare)
  • Barthélemy, Nicolas RWashington University in St. Louis (författare)
  • Vanbrabant, JeroenADx NeuroSciences (författare)
  • Stoops, ErikADx NeuroSciences (författare)
  • Vanmechelen, EugeenADx NeuroSciences (författare)
  • He, YingxinWashington University in St. Louis (författare)
  • Dolado, Anna OrduñaLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)an3874or (författare)
  • Triana-Baltzer, GallenJanssen Pharmaceuticals, US (författare)
  • Pontecorvo, Michael JEli Lilly and Company (författare)
  • Zetterberg, Henrik,1973University of Gothenburg,Lund University,Lunds universitet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,University College London,Sahlgrenska University Hospital,Hong Kong Center for Neurodegenerative Diseases(Swepub:lu)med-hiz (författare)
  • Kolb, HartmuthJanssen Pharmaceuticals, US (författare)
  • Vandijck, ManuFujirebio Europe N.V. (författare)
  • Blennow, Kaj,1958University of Gothenburg,Lund University,Lunds universitet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Sahlgrenska University Hospital(Swepub:lu)med-kbw (författare)
  • Bateman, Randall JWashington University in St. Louis (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:Brain : a journal of neurology: Oxford University Press (OUP)146:4, s. 1592-16011460-21560006-8950
  • Ingår i:Brain: Oxford University Press (OUP)146:4, s. 1592-16010006-8950

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