期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-23746-0
关键词
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资金
- Swedish Research Council [2016-00906]
- Knut and Alice Wallenberg foundation [2017-0383]
- Medical Faculty at Lund University
- Region Skane
- Marianne and Marcus Wallenberg foundation [2015.0125]
- Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson's disease) at Lund University
- Swedish Alzheimer Foundation [AF-745911, AF-930655]
- Swedish Brain Foundation [FO2019-0326, FO2019-0029]
- Parkinson Foundation of Sweden [1280/20]
- Skane University Hospital Foundation [2020-O000028]
- Swedish federal government under the ALF agreement [2018-Projekt0279]
- Stiftelsen Gamla Tjanarinnor [2019-00845]
- EU Joint Programme - Neurodegenerative Disease Research [2019-03401]
- Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse
- Bundy Academy
- Regionalt Forskningsstod [2020-0314]
Plasma biomarkers of amyloid, tau, and neurodegeneration (ATN) can predict clinical deterioration in cognitively unimpaired elderly individuals. A combination of these biomarkers in plasma can reduce the required sample size in clinical trials, making them more feasible and cost-effective while improving efficacy.
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-beta (A beta)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-2 = 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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