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Cited by 199Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsParkinson's Disease Mechanisms and Treatments

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

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Chouliaras, Leonidas, Thomas, Alan, Malpetti, Maura, Donaghy, Paul, Kane, Joseph, Mak, Elijah, Savulich, George, Prats-Sedano, Maria A +5 more·2022·Journal of Neurology, Neurosurgery & Psychiatry
DOI 10.1136/jnnp-2021-327788PMC PMC9148982
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Abstract

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.

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Authors
Chouliaras, L., Thomas, A., Malpetti, M., Donaghy, P., Kane, J., Mak, E., Savulich, G., Prats-Sedano, M. A., Heslegrave, A. J., Zetterberg, H., Su, L., Rowe, J. B., & O'Brien, J. T.
Affiliations
  • University of Cambridge (GB)
  • Newcastle University (GB)
  • Queen's University Belfast (GB)
  • UCL Queen Square Institute of Neurology (GB)
  • Sahlgrenska University Hospital (SE)
Corresponding author
Chouliaras, Leonidas
ORCID
Venue
Journal of Neurology, Neurosurgery & Psychiatry
Publisher
BMJ
Published
2022-01-25
Volume
93
Issue
6
Pages
651-658
ISSN
  • 0022-3050 (ISSN-L)
  • 1468-330X
DOI
10.1136/jnnp-2021-327788
PMC
PMC9148982
OpenAlex
W4207083026
Cited by
199
References
11
Citations by year
2026: 34 · 2025: 58 · 2024: 50 · 2023: 31 · 2022: 26
FWCI
27.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neurology Neurosurgery & Psychiatry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (Queen's University Belfast) (publishedVersion, cc-by)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • Swedish State Support for Clinical Research (ALFGBG-720931)
  • Wellcome (103838)
  • Cambridge Centre for Parkinson-Plus (No grant/award number)
  • Swedish Research Council (681712)
  • UK Dementia Research Institute (No grant/award number)
  • Alzheimer's Drug Discovery Foundation (201809-2016862)
  • National Institute for Health Research (Biomedical Research Centre at Cambridge University, Newcastle Biomedical Research Centre (No grant/awa)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
plasma biomarkers, neurodegeneration, dementia with Lewy bodies, Alzheimer's disease, frontotemporal dementia, progressive supranuclear palsy, phosphorylated tau 181, amyloid-beta, neurofilament light chain, glial fibrillary acidic protein, mild cognitive impairment, differential diagnosis of dementia, cognitive decline, amyloid PET
MeSH terms
Alzheimer Disease, Glial Fibrillary Acidic Protein, Humans, Longitudinal Studies, Supranuclear Palsy, Progressive, Biomarkers, Amyloid beta-Peptides, tau Proteins, Neurodegenerative Diseases, Lewy Body Disease, Frontotemporal Dementia, Cognitive Dysfunction

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