title: Distinct Lysosomal Network Protein Profiles in Parkinsonian Syndrome Cerebrospinal Fluid.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Experimental Pathology, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.|Translational Neuropharmacology, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Boman
authors.affiliation: Developmental Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.|CBD Solutions, Stockholm, Sweden.
authors.forename: Samuel
authors.initials: S
authors.lastname: Svensson
authors.affiliation: Memory and Aging Center, University of California, San Francisco, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Boxer
authors.affiliation: Memory and Aging Center, University of California, San Francisco, USA.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Rojas
authors.affiliation: Memory and Aging Center, University of California, San Francisco, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.affiliation: Memory and Aging Center, University of California, San Francisco, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Karydas
authors.affiliation: Memory and Aging Center, University of California, San Francisco, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Miller
authors.affiliation: Experimental Pathology, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kågedal
authors.affiliation: Translational Neuropharmacology, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2 / Q000134:cerebrospinal fluid; D051907:Lysosomal Membrane Proteins / Q000134:cerebrospinal fluid; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000134:cerebrospinal fluid; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D013494:Supranuclear Palsy, Progressive / Q000134:cerebrospinal fluid / Q000175:diagnosis; D024801:Tauopathies / Q000134:cerebrospinal fluid / Q000175:diagnosis; D033921:Vesicular Transport Proteins / Q000134:cerebrospinal fluid; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D015415:Biomarkers; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D008869:Microtubule-Associated Proteins; D033921:Vesicular Transport Proteins; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C497811:LAMP2 protein, human; C477012:MAP1LC3A protein, human; C093846:early endosome antigen 1
keywords: Biomarkers; CSF; corticobasal degeneration (CBD); parkinson’s disease (PD); progressive supranuclear palsy (PSP)