Distinct Lysosomal Network Protein Profiles in Parkinsonian Syndrome Cerebrospinal Fluid

J Parkinsons Dis. 2016 Apr 2;6(2):307-15. doi: 10.3233/JPD-150759.

Abstract

Background: Clinical diagnosis of parkinsonian syndromes like Parkinson's disease (PD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) is hampered by overlapping symptomatology and lack of diagnostic biomarkers, and definitive diagnosis is only possible post-mortem.

Objective: Since impaired protein degradation plays an important role in many neurodegenerative disorders, we hypothesized that profiles of select lysosomal network proteins in cerebrospinal fluid could be differentially expressed in these parkinsonian syndromes.

Methods: Cerebrospinal fluid samples were collected from PD patients (n = 18), clinically diagnosed 4-repeat tauopathy patients; corticobasal syndrome (CBS) (n = 3) and PSP (n = 8); and pathologically diagnosed PSP (n = 8) and CBD patients (n = 7). Each patient set was compared to its appropriate control group consisting of age and gender matched individuals. Select lysosomal network protein levels were detected via Western blotting. Factor analysis was used to test the diagnostic sensitivity, specificity and accuracy of the select lysosomal network protein expression profiles.

Results: PD, CBD and PSP were markedly different in their cerebrospinal fluid lysosomal network protein profiles. Lysosomal-associated membrane proteins 1 and 2 were significantly decreased in PD; early endosomal antigen 1 was decreased and lysozyme increased in PSP; and lysosomal-associated membrane proteins 1 and 2, microtubule-associated protein 1 light chain 3 and lysozyme were increased in CBD. A panel of lysosomal-associated membrane protein 2, lysozyme and microtubule-associated protein 1 light chain discriminated between controls, PD and 4-repeat tauopathies.

Conclusions: This study offers proof of concept that select lysosomal network proteins are differentially expressed in cerebrospinal fluid of Parkinson's disease, corticobasal syndrome and progressive supranuclear palsy. Lysosomal network protein analysis could be further developed as a diagnostic fluid biomarker in parkinsonian syndromes.

Keywords: Biomarkers; CSF; corticobasal degeneration (CBD); parkinson’s disease (PD); progressive supranuclear palsy (PSP).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / cerebrospinal fluid
  • Female
  • Humans
  • Lysosomal-Associated Membrane Protein 2 / cerebrospinal fluid
  • Lysosome-Associated Membrane Glycoproteins / cerebrospinal fluid
  • Lysosomes / metabolism*
  • Male
  • Microtubule-Associated Proteins / cerebrospinal fluid
  • Middle Aged
  • Parkinsonian Disorders / cerebrospinal fluid*
  • Parkinsonian Disorders / diagnosis
  • Supranuclear Palsy, Progressive / cerebrospinal fluid
  • Supranuclear Palsy, Progressive / diagnosis
  • Tauopathies / cerebrospinal fluid
  • Tauopathies / diagnosis
  • Vesicular Transport Proteins / cerebrospinal fluid

Substances

  • Biomarkers
  • LAMP1 protein, human
  • LAMP2 protein, human
  • Lysosomal-Associated Membrane Protein 2
  • Lysosome-Associated Membrane Glycoproteins
  • Microtubule-Associated Proteins
  • Vesicular Transport Proteins
  • early endosome antigen 1
  • light chain 3, human