Differential levels of plasma biomarkers of neurodegeneration in Lewy body dementia, Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy.
Prats-Sedano, Maria A
Heslegrave, Amanda J
O'Brien, John Tiernan
J Neurol Neurosurg Psychiatry
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Chouliaras, L., Thomas, A., Malpetti, M., Donaghy, P., Kane, J., Mak, E., Savulich, G., et al. (2022). Differential levels of plasma biomarkers of neurodegeneration in Lewy body dementia, Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy.. J Neurol Neurosurg Psychiatry https://doi.org/10.1136/jnnp-2021-327788
OBJECTIVES: This longitudinal study compared emerging plasma biomarkers for neurodegenerative disease between controls, patients with Alzheimer's disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP). METHODS: Plasma phosphorylated tau at threonine-181 (p-tau181), amyloid beta (Αβ)42, Aβ40, neurofilament light (NfL) and glial fibrillar acidic protein (GFAP) were measured using highly sensitive single molecule immunoassays (Simoa) in a multicentre cohort of 300 participants (controls=73, amyloid positive mild cognitive impairment (MCI+) and AD dementia=63, LBD=117, FTD=28, PSP=19). LBD participants had known positron emission tomography (PET)-Aβ status. RESULTS: P-tau181 was elevated in MCI+AD compared with all other groups. Aβ42/40 was lower in MCI+AD compared with controls and FTD. NfL was elevated in all dementias compared with controls while GFAP was elevated in MCI+AD and LBD. Plasma biomarkers could classify between MCI+AD and controls, FTD and PSP with high accuracy but showed limited ability in differentiating MCI+AD from LBD. No differences were detected in the levels of plasma biomarkers when comparing PET-Aβ positive and negative LBD. P-tau181, NfL and GFAP were associated with baseline and longitudinal cognitive decline in a disease specific pattern. CONCLUSION: This large study shows the role of plasma biomarkers in differentiating patients with different dementias, and at monitoring longitudinal change. We confirm that p-tau181 is elevated in MCI+AD, versus controls, FTD and PSP, but is less accurate in the classification between MCI+AD and LBD or detecting amyloid brain pathology in LBD. NfL was elevated in all dementia groups, while GFAP was elevated in MCI+AD and LBD.
Neurodegeneration, 1506, alzheimer's disease, lewy body dementia, frontotemporal dementia, dementia, movement disorders
b. Funding This study was funded by the Cambridge Centre for Parkinson-Plus, the National Institute for Health Research (NIHR) Biomedical Research Centre at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge and the NIHR Newcastle Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The UK Dementia Research Institute, receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the UK Dementia Research Institute at UCL, the Wellcome Trust and an anonymous donor.
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Wellcome Trust (220258/Z/20/Z)
Medical Research Council (MR/M009041/1)
National Institute for Health Research (IS-BRC-1215-20014)
External DOI: https://doi.org/10.1136/jnnp-2021-327788
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333461