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Prediction of future Alzheimer’s disease dementia using plasma phospho-tau combined with other accessible measures

Palmqvist, Sebastian LU orcid ; Tideman, Pontus LU ; Cullen, Nicholas LU ; Zetterberg, Henrik LU ; Blennow, Kaj LU ; Dage, Jeffery L. ; Stomrud, Erik LU orcid ; Janelidze, Shorena LU ; Mattsson-Carlgren, Niklas LU orcid and Hansson, Oskar LU orcid (2021) In Nature Medicine 27(6). p.1034-1042
Abstract

A combination of plasma phospho-tau (P-tau) and other accessible biomarkers might provide accurate prediction about the risk of developing Alzheimer’s disease (AD) dementia. We examined this in participants with subjective cognitive decline and mild cognitive impairment from the BioFINDER (n = 340) and Alzheimer’s Disease Neuroimaging Initiative (ADNI) (n = 543) studies. Plasma P-tau, plasma Aβ42/Aβ40, plasma neurofilament light, APOE genotype, brief cognitive tests and an AD-specific magnetic resonance imaging measure were examined using progression to AD as outcome. Within 4 years, plasma P-tau217 predicted AD accurately (area under the curve (AUC) = 0.83) in BioFINDER. Combining plasma P-tau217, memory, executive function and APOE... (More)

A combination of plasma phospho-tau (P-tau) and other accessible biomarkers might provide accurate prediction about the risk of developing Alzheimer’s disease (AD) dementia. We examined this in participants with subjective cognitive decline and mild cognitive impairment from the BioFINDER (n = 340) and Alzheimer’s Disease Neuroimaging Initiative (ADNI) (n = 543) studies. Plasma P-tau, plasma Aβ42/Aβ40, plasma neurofilament light, APOE genotype, brief cognitive tests and an AD-specific magnetic resonance imaging measure were examined using progression to AD as outcome. Within 4 years, plasma P-tau217 predicted AD accurately (area under the curve (AUC) = 0.83) in BioFINDER. Combining plasma P-tau217, memory, executive function and APOE produced higher accuracy (AUC = 0.91, P < 0.001). In ADNI, this model had similar AUC (0.90) using plasma P-tau181 instead of P-tau217. The model was implemented online for prediction of the individual probability of progressing to AD. Within 2 and 6 years, similar models had AUCs of 0.90–0.91 in both cohorts. Using cerebrospinal fluid P-tau, Aβ42/Aβ40 and neurofilament light instead of plasma biomarkers did not improve the accuracy significantly. The clinical predictions by memory clinic physicians had significantly lower accuracy (4-year AUC = 0.71). In summary, plasma P-tau, in combination with brief cognitive tests and APOE genotyping, might greatly improve the diagnostic prediction of AD and facilitate recruitment for AD trials.

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type
Contribution to journal
publication status
published
subject
in
Nature Medicine
volume
27
issue
6
pages
9 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85106610247
  • pmid:34031605
ISSN
1078-8956
DOI
10.1038/s41591-021-01348-z
language
English
LU publication?
yes
id
a10fe287-0414-45d3-8d3f-6f3ca60da71a
date added to LUP
2021-06-15 16:06:49
date last changed
2024-04-20 08:32:01
@article{a10fe287-0414-45d3-8d3f-6f3ca60da71a,
  abstract     = {{<p>A combination of plasma phospho-tau (P-tau) and other accessible biomarkers might provide accurate prediction about the risk of developing Alzheimer’s disease (AD) dementia. We examined this in participants with subjective cognitive decline and mild cognitive impairment from the BioFINDER (n = 340) and Alzheimer’s Disease Neuroimaging Initiative (ADNI) (n = 543) studies. Plasma P-tau, plasma Aβ42/Aβ40, plasma neurofilament light, APOE genotype, brief cognitive tests and an AD-specific magnetic resonance imaging measure were examined using progression to AD as outcome. Within 4 years, plasma P-tau217 predicted AD accurately (area under the curve (AUC) = 0.83) in BioFINDER. Combining plasma P-tau217, memory, executive function and APOE produced higher accuracy (AUC = 0.91, P &lt; 0.001). In ADNI, this model had similar AUC (0.90) using plasma P-tau181 instead of P-tau217. The model was implemented online for prediction of the individual probability of progressing to AD. Within 2 and 6 years, similar models had AUCs of 0.90–0.91 in both cohorts. Using cerebrospinal fluid P-tau, Aβ42/Aβ40 and neurofilament light instead of plasma biomarkers did not improve the accuracy significantly. The clinical predictions by memory clinic physicians had significantly lower accuracy (4-year AUC = 0.71). In summary, plasma P-tau, in combination with brief cognitive tests and APOE genotyping, might greatly improve the diagnostic prediction of AD and facilitate recruitment for AD trials.</p>}},
  author       = {{Palmqvist, Sebastian and Tideman, Pontus and Cullen, Nicholas and Zetterberg, Henrik and Blennow, Kaj and Dage, Jeffery L. and Stomrud, Erik and Janelidze, Shorena and Mattsson-Carlgren, Niklas and Hansson, Oskar}},
  issn         = {{1078-8956}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  pages        = {{1034--1042}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{Prediction of future Alzheimer’s disease dementia using plasma phospho-tau combined with other accessible measures}},
  url          = {{http://dx.doi.org/10.1038/s41591-021-01348-z}},
  doi          = {{10.1038/s41591-021-01348-z}},
  volume       = {{27}},
  year         = {{2021}},
}