Neuropathology and Cellular Pathogenesis of Spinocerebellar Ataxia Type 12

Movement Disorders : Official Journal of the Movement Disorder Society
E E O'HearnRussell L Margolis

Abstract

SCA12 is a progressive autosomal-dominant disorder, caused by a CAG/CTG repeat expansion in PPP2R2B on chromosome 5q32, and characterized by tremor, gait ataxia, hyperreflexia, dysmetria, abnormal eye movements, anxiety, depression, and sometimes cognitive impairment. Neuroimaging has demonstrated cerebellar and cortical atrophy. We now present the neuropathology of the first autopsied SCA12 brain and utilize cell models to characterize potential mechanisms of SCA12 neurodegeneration. A fixed SCA12 brain was examined using gross, microscopic, and immunohistochemical methods. The effect of the repeat expansion on PPP2R2B Bβ1 expression was examined in multiple cell types by transient transfection of constructs containing the PPP2R2B Bβ1 promoter region attached to a luciferase reporter. The neurotoxic effect of PPP2R2B overexpression was examined in transfected rat primary neurons. Neuropathological investigation revealed enlarged ventricles, marked cerebral cortical atrophy and Purkinje cell loss, less-prominent cerebellar and pontine atrophy, and neuronal intranuclear ubiquitin-positive inclusions, consistent with Marinesco bodies, which did not stain for long polyglutamine tracts, alpha-synuclein, tau, or transactive response...Continue Reading

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Citations

Jul 16, 2016·The Clinical Neuropsychologist·Erin E RobertsonJoan A O'Keefe
Mar 14, 2019·CNS & Neurological Disorders Drug Targets·Laszlo SzpisjakLaszlo Vecsei
Nov 14, 2019·The EMBO Journal·Bart SwinnenLudo Van Den Bosch
Nov 3, 2016·Current Opinion in Neurology·Rachael L Cohen, Russell L Margolis
Jun 26, 2018·Brain : a Journal of Neurology·Marc Corral-JuanAntoni Matilla-Dueñas
Nov 20, 2016·Brain : a Journal of Neurology·Achal K SrivastavaMohammed Faruq
Jul 16, 2020·The Cerebellum·Elan D Louis, Phyllis L Faust
Feb 25, 2021·Journal of Neurology·Melanie Alpaugh, Francesca Cicchetti
Aug 1, 2020·Progress in Retinal and Eye Research·Michael P FautschAlice E Davidson
Jul 27, 2021·Movement Disorders Clinical Practice·Sakhi BhansaliHrishikesh Kumar

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