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Differential levels of plasma biomarkers of neurodegeneration in Lewy body dementia, Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy

Lookup NU author(s): Professor Alan ThomasORCiD, Dr Paul Donaghy, Dr Joseph Kane, Professor John O'Brien



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. 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.

Publication metadata

Author(s): Chouliaras L, Thomas A, Malpetti M, Donaghy P, Kane J, Mak E, Savulich G, Prats-Sedano MA, Heslegrave AJ, Zetterberg H, Su L, Rowe JB, O'Brien JT

Publication type: Article

Publication status: Published

Journal: Journal of Neurology, Neurosurgery, and Psychiatry

Year: 2022

Volume: 93

Issue: 6

Pages: 651-658

Print publication date: 01/06/2022

Online publication date: 25/01/2022

Acceptance date: 01/12/2021

Date deposited: 08/09/2022

ISSN (print): 0022-3050

ISSN (electronic): 1468-330X

Publisher: BMJ Publishing Group


DOI: 10.1136/jnnp-2021-327788

PubMed id: 35078917


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Funder referenceFunder name
NIHR Newcastle Biomedical Research Centre