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Plasma epidermal growth factor levels predict cognitive decline in Parkinson disease

Authors

  • Alice S. Chen-Plotkin MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • William T. Hu MD, PhD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA
    3. Department of Neurology, Emory University School of Medicine, Atlanta, GA
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  • Andrew Siderowf MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Daniel Weintraub MD,

    1. Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Rachel Goldmann Gross MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Howard I. Hurtig MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Sharon X. Xie PhD,

    1. Department Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Steven E. Arnold MD,

    1. Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Murray Grossman MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Christopher M. Clark MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Leslie M. Shaw PhD,

    1. Department Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Leo McCluskey MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Lauren Elman MD,

    1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Vivianna M. Van Deerlin MD, PhD,

    1. Department Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Virginia M.-Y. Lee PhD,

    1. Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Department Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
    3. Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Holly Soares PhD,

    1. Pfizer Global Research and Development, Groton, CT
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  • John Q. Trojanowski MD, PhD

    Corresponding author
    1. Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Department Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA
    3. Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA
    • Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, HUP, Maloney 3rd Floor, 36th and Spruce Streets, Philadelphia, PA 19104-4283
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Abstract

Objective

Most people with Parkinson disease (PD) eventually develop cognitive impairment (CI). However, neither the timing of onset nor the severity of cognitive symptoms can be accurately predicted. We sought plasma-based biomarkers for CI in PD.

Methods

A discovery cohort of 70 PD patients was recruited. Cognitive status was evaluated with the Mattis Dementia Rating Scale-2 (DRS) at baseline and on annual follow-up visits, and baseline plasma levels of 102 proteins were determined with a bead-based immunoassay. Using linear regression, we identified biomarkers of CI in PD, that is, proteins whose levels correlated with cognitive performance at baseline and/or cognitive decline at follow-up. We then replicated the association between cognitive performance and levels of the top biomarker, using a different technical platform, with a separate cohort of 113 PD patients.

Results

Eleven proteins exhibited plasma levels correlating with baseline cognitive performance in the discovery cohort. The best candidate was epidermal growth factor (EGF, p < 0.001); many of the other 10 analytes covaried with EGF across samples. Low levels of EGF not only correlated with poor cognitive test scores at baseline, but also predicted an 8-fold greater risk of cognitive decline to dementia-range DRS scores at follow-up for those with intact baseline cognition. A weaker, but still significant, relationship between plasma EGF levels and cognitive performance was found in an independent replication cohort of 113 PD patients.

Interpretation

Our data suggest that plasma EGF may be a biomarker for progression to CI in PD. Ann Neurol 2010

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