CSF tau and tau/Aβ42 predict cognitive decline in Parkinson's disease.

Abstract

INTRODUCTION:

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: Changqin Liu, Brenna Cholerton, Min Shi, Carmen Ginghina, Kevin C Cain, Peggy Auinger, Parkinson Study Group DATATOP Investigators, Jing Zhang
• Journal: Parkinsonism & related disorders (Parkinsonism Relat Disord) Vol. 21 Issue 3 Pg. 271-6 (Mar 2015) ISSN: 1873-5126 [Electronic] England
• PMID: 25596881 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Antioxidants
• Apolipoproteins E
• Monoamine Oxidase Inhibitors
• Peptide Fragments
• amyloid beta-protein (1-42)
• tau Proteins
• Vitamin E
• Selegiline

Topics

• Adult
• Aged
• Amyloid beta-Peptides (cerebrospinal fluid)
• Antioxidants (therapeutic use)
• Apolipoproteins E (genetics)
• Cognition Disorders (cerebrospinal fluid, diagnosis, drug therapy)
• Cohort Studies
• Cross-Sectional Studies
• Female
• Humans
• Linear Models
• Male
• Middle Aged
• Monoamine Oxidase Inhibitors (therapeutic use)
• Neuropsychological Tests
• Parkinson Disease (complications, drug therapy, genetics)
• Peptide Fragments (cerebrospinal fluid)
• Predictive Value of Tests
• Selegiline (therapeutic use)
• Severity of Illness Index
• Time Factors
• Vitamin E (therapeutic use)
• tau Proteins (cerebrospinal fluid)