Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Plasma phosphorylated tau 217 in preclinical Alzheimer's disease

Jonaitis, Erin M. ; Janelidze, Shorena LU ; Cody, Karly A. ; Langhough, Rebecca ; Du, Lianlian ; Chin, Nathaniel A. ; Mattsson-Carlgren, Niklas LU orcid ; Hogan, Kirk J. ; Christian, Bradley T. and Betthauser, Tobey J. , et al. (2023) In Brain Communications 5(2).
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... (More)

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 ( = 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 (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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, amyloid beta, cognitively unimpaired, plasma, pTau
in
Brain Communications
volume
5
issue
2
article number
fcad057
publisher
Oxford University Press
external identifiers
  • pmid:37013174
  • scopus:85153184229
ISSN
2632-1297
DOI
10.1093/braincomms/fcad057
language
English
LU publication?
yes
id
337dc554-133d-4af0-93fd-c0bd4169d46f
date added to LUP
2023-07-14 14:56:46
date last changed
2024-04-19 23:32:21
@article{337dc554-133d-4af0-93fd-c0bd4169d46f,
  abstract     = {{<p>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 ( = 0.83 (0.75, 0.90), P &lt; 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 (pTau×age =-0.07 (-0.09,-0.06), P &lt; 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.</p>}},
  author       = {{Jonaitis, Erin M. and Janelidze, Shorena and Cody, Karly A. and Langhough, Rebecca and Du, Lianlian and Chin, Nathaniel A. and Mattsson-Carlgren, Niklas and Hogan, Kirk J. and Christian, Bradley T. and Betthauser, Tobey J. and Hansson, Oskar and Johnson, Sterling C.}},
  issn         = {{2632-1297}},
  keywords     = {{Alzheimer's disease; amyloid beta; cognitively unimpaired; plasma; pTau}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{Oxford University Press}},
  series       = {{Brain Communications}},
  title        = {{Plasma phosphorylated tau 217 in preclinical Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1093/braincomms/fcad057}},
  doi          = {{10.1093/braincomms/fcad057}},
  volume       = {{5}},
  year         = {{2023}},
}