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WFRF:(Valentin Marie Anne)
 

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  • Thijssen, Elisabeth HAcademic Medical Center of University of Amsterdam (AMC),University of California, San Francisco (author)

Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study.

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/310879
  • https://gup.ub.gu.se/publication/310879URI
  • https://doi.org/10.1016/S1474-4422(21)00214-3DOI
  • https://lup.lub.lu.se/record/06f5a1eb-5f8e-418a-b964-007ed63d05c0URI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Plasma tau phosphorylated at threonine 217 (p-tau217) and plasma tau phosphorylated at threonine 181 (p-tau181) are associated with Alzheimer's disease tau pathology. We compared the diagnostic value of both biomarkers in cognitively unimpaired participants and patients with a clinical diagnosis of mild cognitive impairment, Alzheimer's disease syndromes, or frontotemporal lobar degeneration (FTLD) syndromes.In this retrospective multicohort diagnostic performance study, we analysed plasma samples, obtained from patients aged 18-99 years old who had been diagnosed with Alzheimer's disease syndromes (Alzheimer's disease dementia, logopenic variant primary progressive aphasia, or posterior cortical atrophy), FTLD syndromes (corticobasal syndrome, progressive supranuclear palsy, behavioural variant frontotemporal dementia, non-fluent variant primary progressive aphasia, or semantic variant primary progressive aphasia), or mild cognitive impairment; the participants were from the University of California San Francisco (UCSF) Memory and Aging Center, San Francisco, CA, USA, and the Advancing Research and Treatment for Frontotemporal Lobar Degeneration Consortium (ARTFL; 17 sites in the USA and two in Canada). Participants from both cohorts were carefully characterised, including assessments of CSF p-tau181, amyloid-PET or tau-PET (or both), and clinical and cognitive evaluations. Plasma p-tau181 and p-tau217 were measured using electrochemiluminescence-based assays, which differed only in the biotinylated antibody epitope specificity. Receiver operating characteristic analyses were used to determine diagnostic accuracy of both plasma markers using clinical diagnosis, neuropathological findings, and amyloid-PET and tau-PET measures as gold standards. Difference between two area under the curve (AUC) analyses were tested with the Delong test.Data were collected from 593 participants (443 from UCSF and 150 from ARTFL, mean age 64 years [SD 13], 294 [50%] women) between July 1 and Nov 30, 2020. Plasma p-tau217 and p-tau181 were correlated (r=0·90, p<0·0001). Both p-tau217 and p-tau181 concentrations were increased in people with Alzheimer's disease syndromes (n=75, mean age 65 years [SD 10]) relative to cognitively unimpaired controls (n=118, mean age 61 years [SD 18]; AUC=0·98 [95% CI 0·95-1·00] for p-tau217, AUC=0·97 [0·94-0·99] for p-tau181; pdiff=0·31) and in pathology-confirmed Alzheimer's disease (n=15, mean age 73 years [SD 12]) versus pathologically confirmed FTLD (n=68, mean age 67 years [SD 8]; AUC=0·96 [0·92-1·00] for p-tau217, AUC=0·91 [0·82-1·00] for p-tau181; pdiff=0·22). P-tau217 outperformed p-tau181 in differentiating patients with Alzheimer's disease syndromes (n=75) from those with FTLD syndromes (n=274, mean age 67 years [SD 9]; AUC=0·93 [0·91-0·96] for p-tau217, AUC=0·91 [0·88-0·94] for p-tau181; pdiff=0·01). P-tau217 was a stronger indicator of amyloid-PET positivity (n=146, AUC=0·91 [0·88-0·94]) than was p-tau181 (n=214, AUC=0·89 [0·86-0·93]; pdiff=0·049). Tau-PET binding in the temporal cortex was more strongly associated with p-tau217 than p-tau181 (r=0·80 vs r=0·72; pdiff<0·0001, n=230).Both p-tau217 and p-tau181 had excellent diagnostic performance for differentiating patients with Alzheimer's disease syndromes from other neurodegenerative disorders. There was some evidence in favour of p-tau217 compared with p-tau181 for differential diagnosis of Alzheimer's disease syndromes versus FTLD syndromes, as an indication of amyloid-PET-positivity, and for stronger correlations with tau-PET signal. Pending replication in independent, diverse, and older cohorts, plasma p-tau217 and p-tau181 could be useful screening tools to identify individuals with underlying amyloid and Alzheimer's disease tau pathology.US National Institutes of Health, State of California Department of Health Services, Rainwater Charitable Foundation, Michael J Fox foundation, Association for Frontotemporal Degeneration, Alzheimer's Association.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • La Joie, RenaudUniversity of California, San Francisco (author)
  • Strom, AmeliaUniversity of California, San Francisco (author)
  • Fonseca, CorrinaUniversity of California, San Francisco (author)
  • Iaccarino, LeonardoUniversity of California, San Francisco (author)
  • Wolf, AmyUniversity of California, San Francisco (author)
  • Spina, SalvatoreUniversity of California, San Francisco (author)
  • Allen, Isabel EUniversity of California, San Francisco (author)
  • Cobigo, YannUniversity of California, San Francisco (author)
  • Heuer, HilaryUniversity of California, San Francisco (author)
  • VandeVrede, LawrenUniversity of California, San Francisco (author)
  • Proctor, Nicholas KEli Lilly and Company (author)
  • Lago, Argentina LarioUniversity of California, San Francisco (author)
  • Baker, SuzanneLawrence Berkeley National Laboratory (author)
  • Sivasankaran, Rajeev (author)
  • Kieloch, Agnieszka (author)
  • Kinhikar, Arvind (author)
  • Yu, Lili (author)
  • Valentin, Marie-Anne (author)
  • Jeromin, Andreas (author)
  • Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska University Hospital,University College London,Sahlgrenska Academy(Swepub:lu)med-hiz (author)
  • Hansson, OskarLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)mphy-ohn (author)
  • 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 (author)
  • Graham, DanielleBiogen, Inc. (author)
  • Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska University Hospital,Sahlgrenska Academy(Swepub:lu)med-kbw (author)
  • Kramer, Joel H (author)
  • Grinberg, Lea TUniversity of California, San Francisco (author)
  • Seeley, William WUniversity of California, San Francisco (author)
  • Rosen, HowardUniversity of California, San Francisco (author)
  • Boeve, Bradley FMayo Clinic Minnesota (author)
  • Miller, Bruce LUniversity of California, San Francisco (author)
  • Teunissen, Charlotte EAcademic Medical Center of University of Amsterdam (AMC) (author)
  • Rabinovici, Gil DUniversity of California, San Francisco (author)
  • Rojas, Julio CUniversity of California, San Francisco (author)
  • Dage, Jeffrey LEli Lilly and Company (author)
  • Boxer, Adam LUniversity of California, San Francisco (author)
  • Academic Medical Center of University of Amsterdam (AMC)University of California, San Francisco (creator_code:org_t)
  • Advancing Research and Treatment for Frontotemporal Lobar Degeneration investigators

Related titles

  • In:The Lancet. Neurology20:9, s. 739-7521474-44651474-4422

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