Plasma biomarkers of amyloid, tau, axonal, and neuroinflammation pathologies in dementia with Lewy bodies

Alzheimers Res Ther. 2024 Jul 3;16(1):146. doi: 10.1186/s13195-024-01502-y.

Abstract

Background: Increasing evidence supports the use of plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation for diagnosis of dementia. However, their performance for positive and differential diagnosis of dementia with Lewy bodies (DLB) in clinical settings is still uncertain.

Methods: We conducted a retrospective biomarker study in two tertiary memory centers, Paris Lariboisière and CM2RR Strasbourg, France, enrolling patients with DLB (n = 104), Alzheimer's disease (AD, n = 76), and neurological controls (NC, n = 27). Measured biomarkers included plasma Aβ40/Aβ42 ratio, p-tau181, NfL, and GFAP using SIMOA and plasma YKL-40 and sTREM2 using ELISA. DLB patients with available CSF analysis (n = 90) were stratified according to their CSF Aβ profile.

Results: DLB patients displayed modified plasma Aβ ratio, p-tau181, and GFAP levels compared with NC and modified plasma Aβ ratio, p-tau181, GFAP, NfL, and sTREM2 levels compared with AD patients. Plasma p-tau181 best differentiated DLB from AD patients (ROC analysis, area under the curve [AUC] = 0.80) and NC (AUC = 0.78), and combining biomarkers did not improve diagnosis performance. Plasma p-tau181 was the best standalone biomarker to differentiate amyloid-positive from amyloid-negative DLB cases (AUC = 0.75) and was associated with cognitive status in the DLB group. Combining plasma Aβ ratio, p-tau181 and NfL increased performance to identify amyloid copathology (AUC = 0.79). Principal component analysis identified different segregation patterns of biomarkers in the DLB and AD groups.

Conclusions: Amyloid, tau, neurodegeneration and neuroinflammation plasma biomarkers are modified in DLB, albeit with moderate diagnosis performance. Plasma p-tau181 can contribute to identify Aβ copathology in DLB.

Keywords: Alzheimer’s disease; Amyloid pathology; Dementia with Lewy bodies; Plasma biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis
  • Amyloid beta-Peptides* / blood
  • Amyloid beta-Peptides* / cerebrospinal fluid
  • Axons / pathology
  • Biomarkers* / blood
  • Biomarkers* / cerebrospinal fluid
  • Chitinase-3-Like Protein 1 / blood
  • Chitinase-3-Like Protein 1 / cerebrospinal fluid
  • Diagnosis, Differential
  • Female
  • Glial Fibrillary Acidic Protein / blood
  • Glial Fibrillary Acidic Protein / cerebrospinal fluid
  • Humans
  • Lewy Body Disease* / blood
  • Lewy Body Disease* / cerebrospinal fluid
  • Lewy Body Disease* / diagnosis
  • Lewy Body Disease* / pathology
  • Male
  • Membrane Glycoproteins
  • Middle Aged
  • Neurofilament Proteins / blood
  • Neurofilament Proteins / cerebrospinal fluid
  • Neuroinflammatory Diseases / blood
  • Neuroinflammatory Diseases / cerebrospinal fluid
  • Neuroinflammatory Diseases / diagnosis
  • Peptide Fragments / blood
  • Peptide Fragments / cerebrospinal fluid
  • Receptors, Immunologic / blood
  • Retrospective Studies
  • tau Proteins* / blood
  • tau Proteins* / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • GFAP protein, human
  • Glial Fibrillary Acidic Protein
  • MAPT protein, human
  • Membrane Glycoproteins
  • neurofilament protein L
  • Neurofilament Proteins
  • Peptide Fragments
  • Receptors, Immunologic
  • tau Proteins
  • TREM2 protein, human