期刊
NATURE MEDICINE
卷 27, 期 6, 页码 1034-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41591-021-01348-z
关键词
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资金
- Swedish Research Council [2016-00906, 2018-02052, 2017-00915, 2018-02532]
- Knut and Alice Wallenberg Foundation [2017-0383]
- 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-940046, AF-742881]
- Swedish Brain Foundation [FO2019-0326, FO2020-0271]
- Parkinson Foundation of Sweden [1280/20]
- Skane University Hospital Foundation [2020-O000028, 2020-0383]
- Swedish federal government under the ALF agreement [2018-Projekt0279, 2018-Projekt0226]
- European Research Council [681712]
- Swedish State Support for Clinical Research [ALFGBG-720931]
- Alzheimer Drug Discovery Foundation, USA [RDAPB-201809-2016615]
- Alzheimer's Association [ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C]
- European Union's Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie grant [860197]
- UK Dementia Research Institute at University College London
- Hjarnfonden, Sweden [FO2017-0243]
- Swedish government [ALFGBG-715986]
- County Councils, the ALF agreement [ALFGBG-715986]
- European Union Joint Program for Neurodegenerative Disorders [JPND2019-466-236]
- GE Healthcare
- Alzheimer's Disease Neuroimaging Initiative (National Institutes of Health) [U01 AG024904]
- Department of Defense [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica
- Biogen
- Bristol-Myers Squibb Company
- CereSpir
- Eisai
- Elan Pharmaceuticals
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche and its affiliated company
- Genentech
- Fujirebio
- Johnson & Johnson Pharmaceutical Research Development
- Lumosity
- Lundbeck
- Merck Co.
- Meso Scale Diagnostics
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals
- Pfizer
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Cogstate
- Canadian Institutes of Health Research
- Regionalt Forskningsstod [2020-0383, 2020-0314]
- MRC [UKDRI-1003] Funding Source: UKRI
Plasma P-tau, in combination with plasma phospho-tau and other biomarkers, along with clinical tests and APOE genotyping, can accurately predict the risk of Alzheimer's disease dementia, improving diagnostic prediction and facilitating recruitment for clinical trials.
Plasma P-tau, in combination with clinical measures, predicts future Alzheimer's disease dementia in two independent cohorts with high accuracy and is superior to the clinical diagnostic predictions of specialists. 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 A beta 42/A beta 40, 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, A beta 42/A beta 40 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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