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

J Neurol Neurosurg Psychiatry. 2022 Jun;93(6):651-658. doi: 10.1136/jnnp-2021-327788. Epub 2022 Jan 25.


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.

Keywords: alzheimer's disease; dementia; frontotemporal dementia; lewy body dementia; movement disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / diagnosis
  • Amyloid beta-Peptides
  • Biomarkers
  • Cognitive Dysfunction* / diagnosis
  • Frontotemporal Dementia* / diagnosis
  • Glial Fibrillary Acidic Protein
  • Humans
  • Lewy Body Disease* / diagnosis
  • Longitudinal Studies
  • Neurodegenerative Diseases*
  • Supranuclear Palsy, Progressive* / diagnosis
  • tau Proteins


  • Amyloid beta-Peptides
  • Biomarkers
  • Glial Fibrillary Acidic Protein
  • tau Proteins