Plasma biomarkers of Alzheimer’s disease improve prediction of cognitive decline in cognitively unimpaired elderly populations
(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
- Cullen, Nicholas C. LU ; Leuzy, Antoine LU ; Janelidze, Shorena LU ; Palmqvist, Sebastian LU ; Svenningsson, Anna L. LU ; Stomrud, Erik LU ; Dage, Jeffrey L. ; Mattsson-Carlgren, Niklas LU and Hansson, Oskar LU
- organization
- publishing date
- 2021-12
- 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
- 2024-09-08 20:10:17
@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 < 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.</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}}, }