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Longitudinal assessment of tau and amyloid beta in cerebrospinal fluid of Parkinson disease

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Abstract

Tau gene has been consistently associated with the risk of Parkinson disease in recent genome wide association studies. In addition, alterations of the levels of total tau, phosphorylated tau [181P], and amyloid beta 1–42 in cerebrospinal fluid have been reported in patients with sporadic Parkinson disease and asymptomatic carriers of leucine-rich repeat kinase 2 mutations, in patterns that clearly differ from those typically described for patients with Alzheimer disease. To further determine the potential roles of these molecules in Parkinson disease pathogenesis and/or in tracking the disease progression, especially at early stages, the current study assessed all three proteins in 403 Parkinson disease patients enrolled in the DATATOP (Deprenyl and tocopherol antioxidative therapy of parkinsonism) placebo-controlled clinical trial, the largest cohort to date with cerebrospinal fluid samples collected longitudinally. These initially drug-naive patients at early disease stages were clinically evaluated, and cerebrospinal fluid was collected at baseline and then at endpoint, defined as the time at which symptomatic anti-Parkinson disease medications were determined to be required. General linear models were used to test for associations between baseline cerebrospinal fluid biomarker levels or their rates of change and changes in the Unified Parkinson Disease Rating Scale (total or part III motor score) over time. Robust associations among candidate markers are readily noted. Baseline levels of amyloid beta were weakly but negatively correlated with baseline Unified Parkinson Disease Rating Scale total scores. Baseline phosphorylated tau/total tau and phosphorylated tau/amyloid beta were significantly and negatively correlated with the rates of the Unified Parkinson Disease Rating Scale change. While medications (deprenyl and/or tocopherol) did not appear to alter biomarkers appreciably, a weak but significant positive correlation between the rate of change in total tau or total tau/amyloid beta levels and the change of the Unified Parkinson Disease Rating Scale was observed. Notably, these correlations did not appear to be influenced by APOE genotype. These results are one of the very first pieces of evidence suggesting that tau and amyloid beta are critically involved in early Parkinson disease progression, potentially by a different mechanism than that in Alzheimer disease, although their applications as Parkinson disease progression markers will likely require the addition of other proteins.

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Acknowledgments

This work was supported by the Michael J. Fox Foundation, the Parkinson Study Group; and the National Institutes of Health [AG033398, ES004696-5897, ES007033-6364, ES016873, ES019277, NS057567, NS060252, NS062684-6221, and NS082137 to J.Z.]. We thank Dr. Hunter R. Underhill for his kind assistance in the initial data analysis, Dr. Karen Marder, Dr. Lorraine N. Clark, and the Parkinson’s Disease Foundation Weill Family Fund for providing the APOE data for this study. We also deeply appreciate the patients for their generous participation and sample donations.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, University of Washington School of Medicine, HMC Box 359635, 325 9th Ave, Seattle, WA, 98104, USA

    Jing Zhang, Hayley A. Mattison, Changqin Liu, Carmen Ginghina, Tessandra Stewart & Min Shi

  2. Department of Endocrinology and Metabolism, Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China

    Changqin Liu

  3. Department of Neurology, Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Peggy Auinger & Michael P. McDermott

  4. Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Michael P. McDermott

  5. Department of Neurology, University of Chicago Medicine and Biological Sciences, Chicago, IL, USA

    Un Jung Kang

  6. Department of Biostatistics, University of Washington School of Public Health, Seattle, WA, USA

    Kevin C. Cain

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Zhang, J., Mattison, H.A., Liu, C. et al. Longitudinal assessment of tau and amyloid beta in cerebrospinal fluid of Parkinson disease. Acta Neuropathol 126, 671–682 (2013). https://doi.org/10.1007/s00401-013-1121-x

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