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Plasma phosphorylated tau 217 in preclinical Alzheimer’s disease

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Jonaitis, Erin M, Janelidze, Shorena, Cody, Karly A, Langhough, Rebecca, Du, Lianlian, Chin, Nathaniel A, Mattsson-Carlgren, Niklas, Hogan, Kirk J +4 more·2023·Brain Communications
DOI 10.1093/braincomms/fcad057PMC PMC10066514

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Abstract

An accurate blood test for Alzheimer’s disease that is sensitive to preclinical proteinopathy and cognitive decline has clear implications for early detection and secondary prevention. We assessed the performance of plasma phosphorylated tau 217 (pTau217) against brain PET markers of amyloid [[11C]-labelled Pittsburgh compound B (PiB)] and tau ([18F]MK-6240) and its utility for predicting longitudinal cognition. Samples were analysed from a subset of participants with up to 8 years follow-up in the Wisconsin Registry for Alzheimer’s Prevention (WRAP; 2001–present; plasma 2011–present), a longitudinal cohort study of adults from midlife, enriched for parental history of Alzheimer’s disease. Participants were a convenience sample who volunteered for at least one PiB scan, had usable banked plasma and were cognitively unimpaired at first plasma collection. Study personnel who interacted with participants or samples were blind to amyloid status. We used mixed effects models and receiver–operator characteristic curves to assess concordance between plasma pTau217 and PET biomarkers of Alzheimer’s disease and mixed effects models to understand the ability of plasma pTau217 to predict longitudinal performance on WRAP’s preclinical Alzheimer’s cognitive composite (PACC-3). The primary analysis included 165 people (108 women; mean age = 62.9 ± 6.06; 160 still enrolled; 2 deceased; 3 discontinued). Plasma pTau217 was strongly related to PET-based estimates of concurrent brain amyloid (β^ = 0.83 (0.75, 0.90), P < 0.001). Concordance was high between plasma pTau217 and both amyloid PET (area under the curve = 0.91, specificity = 0.80, sensitivity = 0.85, positive predictive value = 0.58, negative predictive value = 0.94) and tau PET (area under the curve = 0.95, specificity = 1, sensitivity = 0.85, positive predictive value = 1, negative predictive value = 0.98). Higher baseline pTau217 levels were associated with worse cognitive trajectories (β^pTau×age = −0.07 (−0.09, −0.06), P < 0.001). In a convenience sample of unimpaired adults, plasma pTau217 levels correlate well with concurrent brain Alzheimer’s disease pathophysiology and with prospective cognitive performance. These data indicate that this marker can detect disease before clinical signs and thus may disambiguate presymptomatic Alzheimer’s disease from normal cognitive ageing.

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  • Detection of Aβ positivity using mass spectrometry %p-tau217 in cognitively normal cohorts appears better than what has been reported when using plasma p-tau217 immunoassays.

    “Detection of Aβ positivity using mass spectrometry %p-tau217 in cognitively normal cohorts appears better than what has been reported when using plasma p-tau217 immunoassays, although this must be confirmed in head-to-head studies22,23,48–50.”

    From Highly accurate blood test for Alzheimer's disease is similar or superior to clinical cerebrospinal fluid tests (2024) · cites this paper as [49]

    The Methods (Plasma methods) identify this study’s pTau217 test as an immunoassay, and the Results (pTau217 threshold estimation) report an AUC of 0.90–0.91 for detecting amyloid-PET positivity in cognitively unimpaired participants. The paper therefore supplies immunoassay performance data, but it does not assess mass-spectrometry %p-tau217 or establish that its performance is better. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Authors
Jonaitis, E. M., Janelidze, S., Cody, K. A., Langhough, R., Du, L., Chin, N. A., Mattsson-Carlgren, N., Hogan, K. J., Christian, B. T., Betthauser, T. J., Hansson, O., & Johnson, S. C.
Affiliations
  • University of Wisconsin–Madison (US)
  • Lund University (SE)
  • Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University , Lund 205 02 , Sweden
Corresponding author
  • Jonaitis, Erin M
  • Hansson, Oskar
ORCID
Venue
Brain Communications
Publisher
Oxford University Press (OUP)
Published
2023-03-02
Volume
5
Issue
2
Pages
fcad057-fcad057
ISSN
2632-1297 (ISSN-L)
DOI
10.1093/braincomms/fcad057
PMC
PMC10066514
OpenAlex
W4323357232
Cited by
124
References
5
Citations by year
2026: 36 · 2025: 47 · 2024: 32 · 2023: 9
FWCI
25.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Communications (publishedVersion, cc-by)
  • medRxiv (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • National Institutes of Health (R01AG027161, RO1AG021155, S10 OD025245-01, UL1TR002375)
  • Alzheimer’s Association Research Foundation (19614533)
  • University of Wisconsin Institute for Clinical and Translational Research
  • Swedish Research Council (2016-00906)
  • Knut and Alice Wallenberg foundation (2017-0383)
  • Marianne and Marcus Wallenberg foundation (2015.0125)
  • Strategic Research Area MultiPark
  • Swedish Alzheimer Foundation (AF-939932)
  • Swedish Brain Foundation (FO2021-0293)
  • Parkinson foundation of Sweden (1280/20)
  • Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse
  • Skåne University Hospital (2020-O000028)
  • Regionalt Forskningsstöd (2020-0314)
  • Swedish (2018-Projekt0279)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
Keywords
preclinical Alzheimer's disease, phosphorylated tau217, plasma biomarkers, blood-based diagnosis, amyloid PET, tau PET, Pittsburgh compound B, [18F]MK-6240, cognitive decline prediction, Wisconsin Registry for Alzheimer's Prevention, early detection of Alzheimer's disease, biomarker concordance

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