title: CSF tau and tau/Aβ42 predict cognitive decline in Parkinson's disease.
abstract: BACKGROUND
  A substantial proportion of patients with Parkinson's disease (PD) have concomitant cognitive dysfunction. Identification of biomarker profiles that predict which PD patients have a greater likelihood for progression of cognitive symptoms is pressingly needed for future treatment and prevention approaches.
  
  
  METHODS
  Subjects were drawn from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, a large clinical trial that enrolled initially untreated PD patients. For the current study, Phase One encompassed trial baseline until just prior to levodopa administration (n = 403), and Phase Two spanned the initiation of levodopa treatment until the end of cognitive follow-up (n = 305). Correlations and linear mixed models were performed to determine cross-sectional and longitudinal associations between baseline amyloid β1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) and measures of memory and executive function. Analyses also considered APOE genotype and tremor- vs. rigidity-dominant phenotype.
  
  
  RESULTS
  No association was found between baseline CSF biomarkers and cognitive test performance during Phase One. However, once levodopa treatment was initiated, higher p-tau and p-tau/Aβ42 predicted subsequent decline on cognitive tasks involving both memory and executive functions. The interactions between biomarkers and cognition decline did not appear to be influenced by levodopa dosage, APOE genotype or motor phenotype.
  
  
  CONCLUSIONS
  The current study has, for the first time, demonstrated the possible involvement of tau species, whose gene (MAPT) has been consistently linked to the risk of PD by genome-wide association studies, in the progression of cognitive symptoms in PD.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA; Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China. Electronic address: liuchangqin@126.com.
authors.forename: Changqin
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA; Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA. Electronic address: bchol@uw.edu.
authors.forename: Brenna
authors.initials: B
authors.lastname: Cholerton
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA. Electronic address: mshi70@uw.edu.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA. Electronic address: ginghina@uw.edu.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ginghina
authors.affiliation: Department of Biostatistics, University of Washington School of Public Health, Seattle, WA, USA. Electronic address: cain@uw.edu.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Cain
authors.affiliation: Department of Neurology, Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. Electronic address: peggy.auinger@chet.rochester.edu.
authors.forename: Peggy
authors.initials: P
authors.lastname: Auinger
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA. Electronic address: zhangj@uw.edu.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D000975:Antioxidants / Q000627:therapeutic use; D001057:Apolipoproteins E / Q000235:genetics; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000188:drug therapy; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D011237:Predictive Value of Tests; D012642:Selegiline / Q000627:therapeutic use; D012720:Severity of Illness Index; D013997:Time Factors; D014810:Vitamin E / Q000627:therapeutic use; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001057:Apolipoproteins E; D008996:Monoamine Oxidase Inhibitors; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D014810:Vitamin E; D012642:Selegiline
keywords: Biomarkers; Cerebrospinal fluid; Cognition; Neuropsychological tests; Parkinson disease; tau proteins