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Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring

Ashton, Nicholas J. ; Janelidze, Shorena LU ; Mattsson-Carlgren, Niklas LU orcid ; Binette, Alexa Pichet LU ; Strandberg, Olof LU ; Brum, Wagner S. ; Karikari, Thomas K. ; González-Ortiz, Fernándo ; Di Molfetta, Guglielmo and Meda, Francisco J. , et al. (2022) In Nature Medicine 28(12). p.2555-2562
Abstract

Blood biomarkers indicative of Alzheimer’s disease (AD) pathology are altered in both preclinical and symptomatic stages of the disease. Distinctive biomarkers may be optimal for the identification of AD pathology or monitoring of disease progression. Blood biomarkers that correlate with changes in cognition and atrophy during the course of the disease could be used in clinical trials to identify successful interventions and thereby accelerate the development of efficient therapies. When disease-modifying treatments become approved for use, efficient blood-based biomarkers might also inform on treatment implementation and management in clinical practice. In the BioFINDER-1 cohort, plasma phosphorylated (p)-tau231 and amyloid-β42/40... (More)

Blood biomarkers indicative of Alzheimer’s disease (AD) pathology are altered in both preclinical and symptomatic stages of the disease. Distinctive biomarkers may be optimal for the identification of AD pathology or monitoring of disease progression. Blood biomarkers that correlate with changes in cognition and atrophy during the course of the disease could be used in clinical trials to identify successful interventions and thereby accelerate the development of efficient therapies. When disease-modifying treatments become approved for use, efficient blood-based biomarkers might also inform on treatment implementation and management in clinical practice. In the BioFINDER-1 cohort, plasma phosphorylated (p)-tau231 and amyloid-β42/40 ratio were more changed at lower thresholds of amyloid pathology. Longitudinally, however, only p-tau217 demonstrated marked amyloid-dependent changes over 4–6 years in both preclinical and symptomatic stages of the disease, with no such changes observed in p-tau231, p-tau181, amyloid-β42/40, glial acidic fibrillary protein or neurofilament light. Only longitudinal increases of p-tau217 were also associated with clinical deterioration and brain atrophy in preclinical AD. The selective longitudinal increase of p-tau217 and its associations with cognitive decline and atrophy was confirmed in an independent cohort (Wisconsin Registry for Alzheimer’s Prevention). These findings support the differential association of plasma biomarkers with disease development and strongly highlight p-tau217 as a surrogate marker of disease progression in preclinical and prodromal AD, with impact for the development of new disease-modifying treatments.

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type
Contribution to journal
publication status
published
subject
in
Nature Medicine
volume
28
issue
12
pages
8 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85143266295
  • pmid:36456833
ISSN
1078-8956
DOI
10.1038/s41591-022-02074-w
language
English
LU publication?
yes
id
7ed2f24e-8d2c-46a0-9331-0b563de083da
date added to LUP
2023-01-30 14:07:39
date last changed
2024-06-24 15:50:34
@article{7ed2f24e-8d2c-46a0-9331-0b563de083da,
  abstract     = {{<p>Blood biomarkers indicative of Alzheimer’s disease (AD) pathology are altered in both preclinical and symptomatic stages of the disease. Distinctive biomarkers may be optimal for the identification of AD pathology or monitoring of disease progression. Blood biomarkers that correlate with changes in cognition and atrophy during the course of the disease could be used in clinical trials to identify successful interventions and thereby accelerate the development of efficient therapies. When disease-modifying treatments become approved for use, efficient blood-based biomarkers might also inform on treatment implementation and management in clinical practice. In the BioFINDER-1 cohort, plasma phosphorylated (p)-tau231 and amyloid-β42/40 ratio were more changed at lower thresholds of amyloid pathology. Longitudinally, however, only p-tau217 demonstrated marked amyloid-dependent changes over 4–6 years in both preclinical and symptomatic stages of the disease, with no such changes observed in p-tau231, p-tau181, amyloid-β42/40, glial acidic fibrillary protein or neurofilament light. Only longitudinal increases of p-tau217 were also associated with clinical deterioration and brain atrophy in preclinical AD. The selective longitudinal increase of p-tau217 and its associations with cognitive decline and atrophy was confirmed in an independent cohort (Wisconsin Registry for Alzheimer’s Prevention). These findings support the differential association of plasma biomarkers with disease development and strongly highlight p-tau217 as a surrogate marker of disease progression in preclinical and prodromal AD, with impact for the development of new disease-modifying treatments.</p>}},
  author       = {{Ashton, Nicholas J. and Janelidze, Shorena and Mattsson-Carlgren, Niklas and Binette, Alexa Pichet and Strandberg, Olof and Brum, Wagner S. and Karikari, Thomas K. and González-Ortiz, Fernándo and Di Molfetta, Guglielmo and Meda, Francisco J. and Jonaitis, Erin M. and Koscik, Rebecca Langhough and Cody, Karly and Betthauser, Tobey J. and Li, Yan and Vanmechelen, Eugeen and Palmqvist, Sebastian and Stomrud, Erik and Bateman, Randall J. and Zetterberg, Henrik and Johnson, Sterling C. and Blennow, Kaj and Hansson, Oskar}},
  issn         = {{1078-8956}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{2555--2562}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring}},
  url          = {{http://dx.doi.org/10.1038/s41591-022-02074-w}},
  doi          = {{10.1038/s41591-022-02074-w}},
  volume       = {{28}},
  year         = {{2022}},
}