Quantification of cerebellar hemispheric purkinje cell linear density: 32 ET cases versus 16 controls

Authors

  • Elan D. Louis MD, MSc,

    Corresponding author
    1. GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA
    2. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    3. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    4. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA
    • Correspondence: Dr. Elan Louis, Unit 198, Neurological Institute, 710 West 168th Street, New York, NY 10032, USA; EDL2@columbia.edu

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  • Rachel Babij BS,

    1. GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA
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  • Michelle Lee BA,

    1. GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA
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  • Etty Cortés MD,

    1. Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, New York, USA
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  • Jean-Paul G. Vonsattel MD

    1. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    2. Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, New York, USA
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  • Funding agencies: This work was supported by R01 NS042859 (National Institutes of Health, Bethesda, MD).

  • The statistical analyses were conducted by Elan Louis.

  • Relevant conflicts of interest/financial disclosures: Nothing to report

ABSTRACT

Although essential tremor (ET) is among the most prevalent neurological diseases, its precise pathogenesis is not understood. Purkinje cell loss has been observed in some studies and is the focus of interest and debate. Expressing these data as Purkinje cells/layer length allows one to adjust for the inherent curved nature of the cerebellar folia. Capitalizing on the Essential Tremor Centralized Brain Repository, we quantified Purkinje cell linear density in cases versus controls. Free-floating 100-μm parasagittal cerebellar hemispheric sections were subjected to rabbit polyclonal anti-Calbindin D28k antibody, and 10 random fields/brain were selected for quantification of Purkinje cells/mm−1 Purkinje cell layer. Purkinje cell linear density was lower in 32 ET cases than in16 controls (1.14 ± 0.32 vs. 1.35 ± 0.31/mm−1, P = 0.03). Purkinje cell linear density was inversely associated with torpedo count (r = −0.38, P = 0.028). The current sample of ET cases demonstrates a reduction in Purkinje cell number relative to that of controls. Greater Purkinje cell axonal remodeling (torpedoes) was found in individuals who had the most Purkinje cell drop out. The role of Purkinje cell loss in the pathogenesis of this disorder merits additional study. © 2013 International Parkinson and Movement Disorder Society

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