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Plasma biomarkers of Alzheimer’s disease improve prediction of cognitive decline in cognitively unimpaired elderly populations

Cullen, Nicholas C. LU ; Leuzy, Antoine LU ; Janelidze, Shorena LU ; Palmqvist, Sebastian LU orcid ; Svenningsson, Anna L. LU orcid ; Stomrud, Erik LU orcid ; Dage, Jeffrey L. ; Mattsson-Carlgren, Niklas LU orcid and Hansson, Oskar LU orcid (2021) In Nature Communications 12(1).
Abstract

Plasma biomarkers of amyloid, tau, and neurodegeneration (ATN) need to be characterized in cognitively unimpaired (CU) elderly individuals. We therefore tested if plasma measurements of amyloid-β (Aβ)42/40, phospho-tau217 (P-tau217), and neurofilament light (NfL) together predict clinical deterioration in 435 CU individuals followed for an average of 4.8 ± 1.7 years in the BioFINDER study. A combination of all three plasma biomarkers and basic demographics best predicted change in cognition (Pre-Alzheimer’s Clinical Composite; R2 = 0.14, 95% CI [0.12–0.17]; P < 0.0001) and subsequent AD dementia (AUC = 0.82, 95% CI [0.77–0.91], P < 0.0001). In a simulated clinical trial, a screening algorithm combining all three plasma... (More)

Plasma biomarkers of amyloid, tau, and neurodegeneration (ATN) need to be characterized in cognitively unimpaired (CU) elderly individuals. We therefore tested if plasma measurements of amyloid-β (Aβ)42/40, phospho-tau217 (P-tau217), and neurofilament light (NfL) together predict clinical deterioration in 435 CU individuals followed for an average of 4.8 ± 1.7 years in the BioFINDER study. A combination of all three plasma biomarkers and basic demographics best predicted change in cognition (Pre-Alzheimer’s Clinical Composite; R2 = 0.14, 95% CI [0.12–0.17]; P < 0.0001) and subsequent AD dementia (AUC = 0.82, 95% CI [0.77–0.91], P < 0.0001). In a simulated clinical trial, a screening algorithm combining all three plasma biomarkers would reduce the required sample size by 70% (95% CI [54–81]; P < 0.001) with cognition as trial endpoint, and by 63% (95% CI [53–70], P < 0.001) with subsequent AD dementia as trial endpoint. Plasma ATN biomarkers show usefulness in cognitively unimpaired populations and could make large clinical trials more feasible and cost-effective.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
12
issue
1
article number
3555
publisher
Nature Publishing Group
external identifiers
  • pmid:34117234
  • scopus:85107693553
ISSN
2041-1723
DOI
10.1038/s41467-021-23746-0
language
English
LU publication?
yes
id
f5fd4fa7-6117-46ee-9b45-a35cb36547f3
date added to LUP
2021-07-01 13:37:19
date last changed
2024-06-16 15:43:10
@article{f5fd4fa7-6117-46ee-9b45-a35cb36547f3,
  abstract     = {{<p>Plasma biomarkers of amyloid, tau, and neurodegeneration (ATN) need to be characterized in cognitively unimpaired (CU) elderly individuals. We therefore tested if plasma measurements of amyloid-β (Aβ)42/40, phospho-tau217 (P-tau217), and neurofilament light (NfL) together predict clinical deterioration in 435 CU individuals followed for an average of 4.8 ± 1.7 years in the BioFINDER study. A combination of all three plasma biomarkers and basic demographics best predicted change in cognition (Pre-Alzheimer’s Clinical Composite; R<sup>2</sup> = 0.14, 95% CI [0.12–0.17]; P &lt; 0.0001) and subsequent AD dementia (AUC = 0.82, 95% CI [0.77–0.91], P &lt; 0.0001). In a simulated clinical trial, a screening algorithm combining all three plasma biomarkers would reduce the required sample size by 70% (95% CI [54–81]; P &lt; 0.001) with cognition as trial endpoint, and by 63% (95% CI [53–70], P &lt; 0.001) with subsequent AD dementia as trial endpoint. Plasma ATN biomarkers show usefulness in cognitively unimpaired populations and could make large clinical trials more feasible and cost-effective.</p>}},
  author       = {{Cullen, Nicholas C. and Leuzy, Antoine and Janelidze, Shorena and Palmqvist, Sebastian and Svenningsson, Anna L. and Stomrud, Erik and Dage, Jeffrey L. and Mattsson-Carlgren, Niklas and Hansson, Oskar}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Plasma biomarkers of Alzheimer’s disease improve prediction of cognitive decline in cognitively unimpaired elderly populations}},
  url          = {{http://dx.doi.org/10.1038/s41467-021-23746-0}},
  doi          = {{10.1038/s41467-021-23746-0}},
  volume       = {{12}},
  year         = {{2021}},
}