title: Mapping Purkinje Cell Placement Along the Purkinje Cell Layer: an Analysis of Postmortem Tissue from Essential Tremor Patients vs. Controls.
abstract: Postmortem studies have reported Purkinje cell loss in essential tremor (ET), and we recently demonstrated a significant increase in the mean distance between Purkinje cell bodies (i.e., a larger gap length distance) in ET cases vs. controls, likely reflecting a disease-associated reduction in Purkinje cells. We now analyze the regularity of distribution of Purkinje cells along the Purkinje cell layer to determine whether there is greater disorganization in ET cases than in age-matched controls. A standard parasagittal, formalin-fixed, tissue block was harvested from the neocerebellum of 50 ET cases and 25 age-matched controls. The gap length distance (μm) between Purkinje cells was quantified using a nearest neighbor analysis in which the distance between each Purkinje cell body was measured in OpenLAB software, version 5 (Improvision, Waltham, MA) by drawing a freehand line between adjacent Purkinje cell bodies along the entirety of the Purkinje cell layer within a given image. We analyzed the subject-specific variation in the organization of Purkinje cells along the Purkinje cell layer. The 50 ET cases and 25 controls were similar in age at death, gender, and brain weight. Overall, greater variation in gap length distance (i.e., more disorganization) was associated with greater gap length distance (p < 0.001) and younger age (p = 0.020). However, the variation in the Purkinje cell gap length distance (i.e., Purkinje cell organization) did not differ in ET cases and controls (p = 0.330). We observed that the regularity of the distribution of Purkinje cells along the Purkinje cell layer did not differ between ET cases and controls. Several alternative biological interpretations for this finding are discussed.
authors.affiliation: Department of Neurology, Yale School of Medicine, Yale University, LCI 710, 15 York Street, PO Box 208018, New Haven, CT, 06520-8018, USA. elan.louis@yale.edu.|Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA. elan.louis@yale.edu.|Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, CT, USA. elan.louis@yale.edu.
authors.forename: Elan D
authors.initials: ED
authors.lastname: Louis
authors.affiliation: Department of Statistics, Columbia University, New York, NY, 10032, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rabinowitz
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, NY, 10032, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Choe
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, NY, 10032, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Tate
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, NY, 10032, USA.
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Kelly
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
authors.forename: Sheng-Han
authors.initials: SH
authors.lastname: Kuo
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, NY, 10032, USA.
authors.forename: Phyllis L
authors.initials: PL
authors.lastname: Faust
mesh_terms: D000369:Aged, 80 and over; D002452:Cell Count; D020329:Essential Tremor / Q000473:pathology*; D005260:Female; D005404:Fixatives; D005557:Formaldehyde; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008853:Microscopy; D011689:Purkinje Cells / Q000166:cytology* / Q000473:pathology*; D012984:Software; D016707:Tissue Fixation
chemical_list: D005404:Fixatives; D005557:Formaldehyde
keywords: Cerebellum; Essential tremor; Neurodegenerative; Purkinje