title: Neurodegenerative CSF markers in genetic and sporadic PD: Classification and prediction in a longitudinal study.
abstract: BACKGROUND
  Parkinson's disease (PD) patients show a large phenotypic variability probably reflecting inter-individual pathologic heterogeneity. Next to typical Lewy-body pathology, β-amyloid (Aβ) and tau pathology have been found at autopsy and several studies have reported altered CSF levels of Aβ1-42, total-Tau (t-Tau) and phosphorylated-Tau (p-Tau).
  
  
  OBJECTIVE
  To evaluate whether CSF levels of neurodegenerative markers are influenced by genetics and whether specific subgroups of PD are more prone to a concomitant pathology possibly reflecting aspects of disease progression.
  
  
  METHODS
  In an explorative study we assessed CSF profiles of Aβ1-42, t-Tau, and p-Tau longitudinally in PD patients carrying LRRK2 (n = 5) or GBA mutations (n = 12), sporadic PD patients (n = 30) and healthy controls (n = 16).
  
  
  RESULTS
  Compared to healthy controls, all three PD cohorts showed lower levels of Aβ1-42. Moreover, sporadic PD and GBA-PD patients presented with lower levels of t-Tau and p-Tau whereas this phenomenon was not seen in LRRK2-PD patients. Regression analyses revealed an association between higher levels of Baseline p-Tau with more accelerated cognitive deterioration over time in LRRK2-PD and GBA-PD patients, but not in sporadic PD.
  
  
  CONCLUSIONS
  PD patients present with disease-specific CSF profiles of Aβ1-42, t-Tau and p-Tau arguing in favor of an involvement of these proteins in PD pathogenesis in both sporadic and genetic forms. Moreover, we found first hints for differences in these CSF profiles between genetically determined PD cohorts but that CSF constellations which tend to predict aspects of disease progression such as cognitive decline seem similar across subgroups of PD.
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. Electronic address: Kathrin.Brockmann@uni-tuebingen.de.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Brockmann
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schulte
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Deuschle
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Hauser
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Heger
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Maetzler
authors.affiliation: Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Berg
mesh_terms: D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000523:psychology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010641:Phenotype; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012044:Regression Analysis; D012720:Severity of Illness Index; D012959:Socioeconomic Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005962:Glucosylceramidase
keywords: Abeta; CSF; GBA; LRRK2; Parkinson; Tau