{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T18:36:18Z","timestamp":1760985378019,"version":"build-2065373602"},"reference-count":23,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2015,10,21]],"date-time":"2015-10-21T00:00:00Z","timestamp":1445385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03c4-pathology in an unique distribution pattern largely restricted to the brainstem. \u03b1-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 \u03c4 pathology and \u03b1-synuclein containing Lewy bodies in our SPG7 cases may be either coincidental or related to SPG7 in addition to neuron loss and  neuritic pathology.<\/jats:p>","DOI":"10.3390\/ijms161025050","type":"journal-article","created":{"date-parts":[[2015,10,22]],"date-time":"2015-10-22T03:05:31Z","timestamp":1445483131000},"page":"25050-25066","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Abnormal Paraplegin Expression in Swollen Neurites,  \u03c4- and \u03b1-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation"],"prefix":"10.3390","volume":"16","author":[{"given":"Dietmar","family":"Thal","sequence":"first","affiliation":[{"name":"Laboratory of Neuropathology\u2014Institute of Pathology, Center of Clinical Research,  University of Ulm, Helmholtzstra\u00dfe 8\/1, D-89081 Ulm, Germany"},{"name":"Department of Neuroscience, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Z\u00fcchner","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics University of  Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Gierer","sequence":"additional","affiliation":[{"name":"Outpatient Praxis for Neurology, D-89407 Dillingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Schulte","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research,  Hoppe-Seyler-Strasse 3, University of T\u00fcbingen, 72077 T\u00fcbingen, Germany"},{"name":"German Research Center for Neurodegenerative Diseases (DZNE), University of T\u00fcbingen,  72076 Tuebingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludger","family":"Sch\u00f6ls","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research,  Hoppe-Seyler-Strasse 3, University of T\u00fcbingen, 72077 T\u00fcbingen, Germany"},{"name":"German Research Center for Neurodegenerative Diseases (DZNE), University of T\u00fcbingen,  72076 Tuebingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Sch\u00fcle","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics University of  Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research,  Hoppe-Seyler-Strasse 3, University of T\u00fcbingen, 72077 T\u00fcbingen, Germany"},{"name":"German Research Center for Neurodegenerative Diseases (DZNE), University of T\u00fcbingen,  72076 Tuebingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2280-7273","authenticated-orcid":false,"given":"Matthis","family":"Synofzik","sequence":"additional","affiliation":[{"name":"Outpatient Praxis for Neurology, D-89407 Dillingen, Germany"},{"name":"Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research,  Hoppe-Seyler-Strasse 3, University of T\u00fcbingen, 72077 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1212\/WNL.0000000000001369","article-title":"SPG7 mutations are a common cause of undiagnosed ataxia","volume":"84","author":"Pfeffer","year":"2015","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1093\/brain\/aws240","article-title":"Spastic paraplegia gene 7 in patients with spasticity and\/or optic neuropathy","volume":"135","author":"Klebe","year":"2012","journal-title":"Brain: J. 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