Using cerebrospinal fluid marker profiles in clinical diagnosis of dementia with Lewy bodies, Parkinson's disease, and Alzheimer's disease

J Alzheimers Dis. 2014;38(1):63-73. doi: 10.3233/JAD-130995.

Abstract

Background: Dementia with Lewy bodies (DLB) is difficult to differentiate from other neuro-degenerative diseases. Patients are often mistaken to suffer from Parkinson's disease (PD) or Alzheimer's disease (AD) because of the overlapping clinical appearances concerning cognition and movement.

Objective: We investigated the possibility for a valid differential diagnosis using cerebrospinal fluid (CSF) biomarkers.

Methods: In the context of a large retrospective study, we analyzed data of patients suffering from degenerative, ischemic, or inflammatory CNS (central nervous system) diseases and identified those with DLB (n = 34), PD (n = 37), and AD (n = 47) for further analyses.

Results: We detected abnormalities in the CSF profiles of those patients with DLB while using a combination of decreased amyloid-β (Aβ)42 and increased tau levels. By stratification of data by disease severity, we observed a high sensitivity of this combination especially in the subgroup of patients with advanced stages, while the sensitivity in early forms was lower. In addition, with clinical deterioration, the abnormalities in the CSF profile became more pronounced.

Conclusion: We conclude that DLB can be distinguished from PD, in spite of both being synucleinopathies, by CSF profiles using neurodegenerative marker analysis. The pathophysiology of increased tau and decreased Aβ levels in those conditions has to be elucidated further, since both proteins are known to be involved in the pathogenesis of AD, but no clear explanation has been postulated for DLB yet.

Keywords: Alzheimer's disease; Parkinson's disease; amyloid-β; cerebrospinal fluid; clinical diagnosis; dementia; dementia with Lewy bodies; tau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Analysis of Variance
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Lewy Body Disease / cerebrospinal fluid*
  • Male
  • Parkinson Disease / cerebrospinal fluid*
  • Peptide Fragments / cerebrospinal fluid*
  • Retrospective Studies
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • tau Proteins