Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation

International Journal of Molecular Sciences

Dietmar R. Thal³  Stephan Z࿌hner¹  Stephan Gierer²  Claudia Schulte⁴  Ludger Schöls⁴  Rebecca Schüle¹  Matthis Synofzik² 

[1] Dr. John T. Macdonald Foundation Department of Human Genetics University of Miami Miller School of Medicine, Miami, FL 33136, USA; E-Mails:;Outpatient Praxis for Neurology, D-89407 Dillingen, Germany; E-Mail:;Laboratory of Neuropathology—Institute of Pathology, Center of Clinical Research, University of Ulm, Helmholtzstraße 8/1, D-89081 Ulm, Germany;Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Hoppe-Seyler-Strasse 3, University of Tübingen, 72077 Tübingen, Germany; E-Mails:

关键词: SPG7;    neurofibrillary tangles;    tau;    spastic paraplegia;    ataxia;    spastic ataxia;    coiled bodies;    Lewy bodies;    paraplegin;   

DOI  :  10.3390/ijms161025050

来源: mdpi

【 摘 要 】

Mutations in the SPG7 gene are the most frequent cause of autosomal recessive hereditary spastic paraplegias and spastic ataxias. Ala510Val is the most common SPG7 mutation, with a frequency of up to 1% in the general population. Here we report the clinical, genetic, and neuropathological findings in a homozygous Ala510Val SPG7 case with spastic ataxia. Neuron loss with associated gliosis was found in the inferior olivary nucleus, the dentate nucleus of the cerebellum, the substantia nigra and the basal nucleus of Meynert. Neurofilament and/or paraplegin accumulation was observed in swollen neurites in the cerebellar and cerebral cortex. This case also showed subcortical τ-pathology in an unique distribution pattern largely restricted to the brainstem. α-synuclein containing Lewy bodies (LBs) were observed in the brainstem and the cortex, compatible with a limbic pattern of Braak LB-Disease stage 4. Taken together, this case shows that the spectrum of pathologies in SPG7 can include neuron loss of the dentate nucleus and the inferior olivary nucleus as well as neuritic pathology. The progressive supranuclear palsy-like brainstem predominant pattern of τ pathology and α-synuclein containing Lewy bodies in our SPG7 cases may be either coincidental or related to SPG7 in addition to neuron loss and neuritic pathology.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.