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Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer's Disease Neuroimaging Initiative.

Author information

Affiliations

  • 1. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
      Authors
    • Karikari TK 1
    • Ashton NJ 1
    • Lantero Rodriguez J 1
    • Snellman A 1
    • Kvartsberg H 1
    • Rial AM 1
    • Andreasson U 1
    • Schöll M 1
    • Blennow K 1
    • Zetterberg H 1
    (10 authors)
  • 2. Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, H4H 1R3, Montreal, QC, Canada.
      Authors
    • Benedet AL 2
    • Lussier F 2
    • Pascoal TA 2
    • Rosa-Neto P 2
    (4 authors)
  • 3. Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
      Authors
    • Suárez-Calvet M 3
    (1 author)
  • 4. Department of Epidemiology and Biostatistics, McGill University, Montreal, QC, Canada.
      Authors
    • Saha-Chaudhuri P 4
    (1 author)
  • 5. Department of Radiology, Medicine, and Psychiatry, University of California San Francisco, San Francisco, CA, USA.
      Authors
    • Weiner MW 5
    (1 author)
    • Show all (7)

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Molecular Psychiatry, 26 Oct 2020, 26(2):429-442
https://doi.org/10.1038/s41380-020-00923-z PMID: 33106600 

This article is based on a previously available preprint.

Abstract 

Whilst cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers for amyloid-β (Aβ) and tau pathologies are accurate for the diagnosis of Alzheimer's disease (AD), their broad implementation in clinical and trial settings are restricted by high cost and limited accessibility. Plasma phosphorylated-tau181 (p-tau181) is a promising blood-based biomarker that is specific for AD, correlates with cerebral Aβ and tau pathology, and predicts future cognitive decline. In this study, we report the performance of p-tau181 in >1000 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including cognitively unimpaired (CU), mild cognitive impairment (MCI) and AD dementia patients characterized by Aβ PET. We confirmed that plasma p-tau181 is increased at the preclinical stage of Alzheimer and further increases in MCI and AD dementia. Individuals clinically classified as AD dementia but having negative Aβ PET scans show little increase but plasma p-tau181 is increased if CSF Aβ has already changed prior to Aβ PET changes. Despite being a multicenter study, plasma p-tau181 demonstrated high diagnostic accuracy to identify AD dementia (AUC = 85.3%; 95% CI, 81.4-89.2%), as well as to distinguish between Aβ- and Aβ+ individuals along the Alzheimer's continuum (AUC = 76.9%; 95% CI, 74.0-79.8%). Higher baseline concentrations of plasma p-tau181 accurately predicted future dementia and performed comparably to the baseline prediction of CSF p-tau181. Longitudinal measurements of plasma p-tau181 revealed low intra-individual variability, which could be of potential benefit in disease-modifying trials seeking a measurable response to a therapeutic target. This study adds significant weight to the growing body of evidence in the use of plasma p-tau181 as a non-invasive diagnostic and prognostic tool for AD, regardless of clinical stage, which would be of great benefit in clinical practice and a large cost-saving in clinical trial recruitment.

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Read article at publisher's site: https://doi.org/10.1038/s41380-020-00923-z

Read article for free, from open access legal sources, via Unpaywall: http://repositori.upf.edu/bitstream/10230/52562/1/karikari-mop-diag.pdfUnpaywall

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Funders who supported this work.

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    Medical Research Council (1)

    NIA NIH HHS (1)