Prediction of future Alzheimer’s disease dementia using plasma phospho-tau combined with other accessible measures
Top Cited Papers
- 24 May 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 27 (6), 1034-1042
- https://doi.org/10.1038/s41591-021-01348-z
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 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.Keywords
Funding Information
- Vetenskapsrådet (2018-02052, 2016-00906)
- Hjärnfonden (FO2020-0271)
- Alzheimerfonden (AF-940046, AF-745911)
- Knut och Alice Wallenbergs Stiftelse (2017-0383)
This publication has 55 references indexed in Scilit:
- Comparison of Brief Cognitive Tests and CSF Biomarkers in Predicting Alzheimer’s Disease in Mild Cognitive Impairment: Six-Year Follow-Up StudyPLOS ONE, 2012
- Amyloid deposition, hypometabolism, and longitudinal cognitive declineAnnals of Neurology, 2012
- Factors affecting Aβ plasma levels and their utility as biomarkers in ADNIActa Neuropathologica, 2011
- Cognitive Impairment Questionnaire (CIMP-QUEST): reported topographic symptoms in MCI and dementiaActa Neurologica Scandinavica, 2010
- The Mayo Clinic Study of Aging: Design and Sampling, Participation, Baseline Measures and Sample CharacteristicsNeuroepidemiology, 2008
- Multimodel InferenceSociological Methods & Research, 2004
- Mild cognitive impairment as a diagnostic entityJournal of Internal Medicine, 2004
- Clinical diagnosis of Alzheimer's diseaseNeurology, 1984
- Measurement of Functional Activities in Older Adults in the CommunityJournal of Gerontology, 1982
- Outcome for survivors of mechanical ventilation weighing less than 1,250 gm at birthThe Journal of Pediatrics, 1981