{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T04:02:19Z","timestamp":1793419339397,"version":"4.5.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T00:00:00Z","timestamp":1727049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Gerstmann\u2013Str\u00e4ussler\u2013Scheinker (GSS) disease is an inherited prion disease characterized by dementia, cerebellar ataxia, and painful sensory disturbances. GSS is pathologically defined by the presence of amyloid plaques comprised of prion protein predominantly localized in the cerebral cortex, cerebellar cortex, and basal ganglia, resulting from mutations in the prion protein gene. This study investigated five cases of GSS P102L [GSS caused by a leucine (L) substitution of proline (P) at position 102 of the prion protein gene] with L-dopa-resistant extrapyramidal symptoms and reduced dopamine transporter single-photon emission computed tomography (DAT-SPECT) uptake. Clinical findings revealed diverse manifestations, with all cases exhibiting parkinsonism, and four patients had a vertical gaze palsy. Notably, all patients showed reduced striatal DAT-SPECT uptake, indicating neurodegeneration of the nigrostriatal system. Autopsy findings in one case confirmed prion protein plaques and dopaminergic neuron loss in the substantia nigra of a patient with GSS P102L. Additionally, reduced DAT immunostaining was observed in the putamen compared with a control. While previous studies have identified reduced DAT-SPECT and positron emission tomography uptake in Creutzfeldt-Jakob disease and fatal familial insomnia owing to nigrostriatal neurodegeneration induced by abnormal prion protein deposition, similar phenomena in GSS P102L have not been reported. This study provides support for a correlation between abnormal prion protein deposition and nigrostriatal system degeneration in GSS P102L. Our results reveal the importance of considering GSS P102L in cases of atypical Parkinsonism and abnormal DAT-SPECT results, which would serve as a valuable indicator for subsequent prion genetic testing.<\/jats:p>","DOI":"10.3389\/fneur.2024.1452709","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T04:29:22Z","timestamp":1727065762000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Dopaminergic neurodegeneration in Gerstmann\u2013Str\u00e4ussler\u2013Scheinker (P102L) disease: insights from imaging and pathological examination"],"prefix":"10.3389","volume":"15","author":[{"given":"Ken-Ichi","family":"Irie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Honda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahisa","family":"Tateishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akifumi","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Morimitsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kikuchi","family":"Shinsuke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiga","family":"Moritaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiji","family":"Kurata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Kumazoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Shijo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naokazu","family":"Sasagasako","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Taniwaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2632","DOI":"10.1093\/brain\/awn202","article-title":"Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series","volume":"131","author":"Webb","year":"2008","journal-title":"Brain"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"3043","DOI":"10.1093\/brain\/awq216","article-title":"Prospective 10-year surveillance of human prion diseases in Japan","volume":"133","author":"Nozaki","year":"2010","journal-title":"Brain"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s40734-019-0082-1","article-title":"A case of Gerstmann-Straussler-Scheinker (GSS) disease with supranuclear gaze palsy","volume":"6","author":"Ufkes","year":"2019","journal-title":"J Clin Mov Disord"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1002\/mdc3.13976","article-title":"Gerstmann-Str\u00e4ussler-Scheinker disease presenting as late-onset slowly progressive spinocerebellar ataxia, and comparative case series with neuropathology","volume":"11","author":"Stephen","year":"2024","journal-title":"Mov Disord Clin Pract"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1212\/01.wnl.0000218211.85675.18","article-title":"Early clinical signs and imaging findings in Gerstmann-Str\u00e4ussler-Scheinker syndrome (Pro102Leu)","volume":"66","author":"Arata","year":"2006","journal-title":"Neurology"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"5157275","DOI":"10.1155\/2018\/5157275","article-title":"Parkinsonism associated with pathological 123I-FP-CIT SPECT (DATSCAN) results as the initial manifestation of sporadic Creutzfeldt-Jakob disease","volume":"2018","author":"Garc\u00eda","year":"2018","journal-title":"Case Rep Neurol Med"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1111\/j.1600-0404.2008.01075.x","article-title":"Striatal [123I] FP-CIT SPECT demonstrates dopaminergic deficit in a sporadic case of Creutzfeldt-Jakob disease","volume":"119","author":"Ragno","year":"2009","journal-title":"Acta Neurol Scand"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"400","DOI":"10.3906\/sag-2008-253","article-title":"Dopamine transporter SPECT imaging in Parkinson\u2019s disease and parkinsoniam disorders","volume":"51","author":"Akdemir","year":"2021","journal-title":"Turk J Med Sci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1080\/19336896.2022.2093078","article-title":"18F-FP-CIT PET\/CT in a case of probable sporadic Creutzfeldt-Jakob disease with parkinsonism as initial symptom","volume":"16","author":"Tang","year":"2022","journal-title":"Prion"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e50594","DOI":"10.7759\/cureus.50594","article-title":"Gerstmann-Str\u00e4ussler-Scheinker syndrome with parkinsonism, Dyskunesia, and Abnomal (I-123)-FP-CIT single-photon emission computed tomography: a case report","volume":"15","author":"Jiang","year":"2023","journal-title":"Cureus"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e400","DOI":"10.1212\/NXG.0000000000000400","article-title":"Gerstmann-Str\u00e4ussler-Scheinker disease (PRNP p. D202N) presenting with atypical parkinsonism","volume":"6","author":"Baiardi","year":"2020","journal-title":"Neurol Genet"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1002\/mdc3.12307","article-title":"Clinicopathological correlates in a PRNP P102L mutation carrier with rapidly progressing parkinsonism-dystonia","volume":"3","author":"Umeh","year":"2016","journal-title":"Mov Disord Clin Pract"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1007\/s00259-006-0155-x","article-title":"Quantification of [123I] FP-CIT SPECT brain images: an accurate technique for measurement of the specific binding ratio","volume":"33","author":"Tossici-Bolt","year":"2006","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1001\/archneur.61.7.1104","article-title":"Frontal assessment battery and differential diagnosis of frontotemporal dementia and Alzheimer disease","volume":"61","author":"Slachevsky","year":"2004","journal-title":"Arch Neurol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1002\/ana.25579","article-title":"Clinical Variability in P102L Gerstmann-Str\u00e4ussler-Scheinker Syndrome","volume":"86","author":"Tesar","year":"2019","journal-title":"Ann Neurol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1007\/s00439-005-0020-1","article-title":"Genetic prion disease: the EUROCJD experience","volume":"118","author":"Kov\u00e1cs","year":"2005","journal-title":"Hum Genet"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e229729","DOI":"10.1136\/bcr-2019-229729","article-title":"Gerstmann-Str\u00e4ussler-Scheinker syndrome misdiagnosed as conversion disorder","volume":"12","author":"Jiang","year":"2019","journal-title":"BMJ Case Rep"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1007\/s12264-021-00764-y","article-title":"Genetic prion disease: insight from the features and experience of China national surveillance for Creutzfeldt-Jakob disease","volume":"37","author":"Shi","year":"2021","journal-title":"Neurosci Bull"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1212\/WNL.0000000000006730","article-title":"Pearls & oy-sters: challenging diagnosis of Gerstmann-Str\u00e4ussler-Scheinker disease: clinical and imaging findings","volume":"92","author":"Kang","year":"2019","journal-title":"Neurology"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e60003","DOI":"10.1371\/journal.pone.0060003","article-title":"Relationships between clinicopathological features and cerebrospinal fluid biomarkers in Japanese patients with genetic prion diseases","volume":"8","author":"Higuma","year":"2013","journal-title":"PLoS One"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1743-422X-8-559","article-title":"An overview of human prion diseases","volume":"8","author":"Imran","year":"2011","journal-title":"Virol J"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1212\/01.wnl.0000256819.61531.98","article-title":"Novel prion protein gene mutation presenting with subacute PSP-like syndrome","volume":"68","author":"Rowe","year":"2007","journal-title":"Neurology"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"216.e1","DOI":"10.1016\/j.neurobiolaging.2016.09.018","article-title":"Clinical features of Chinese patients with Gerstmann-Str\u00e4ussler-Scheinker identified by targeted next-generation sequencing","volume":"49","author":"Li","year":"2017","journal-title":"Neurobiol Aging"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"389","DOI":"10.12998\/wjcc.v7.i3.389","article-title":"Gerstmann-Str\u00e4ussler-Scheinker disease: a case report","volume":"7","author":"Zhao","year":"2019","journal-title":"World J Clin Cases"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1187813","DOI":"10.3389\/fneur.2023.1187813","article-title":"Case report: a Chinese patient with spinocerebellar ataxia finally confirmed as Gerstmann-Str\u00e4ussler-Scheinker syndrome with P102L mutation","volume":"14","author":"Chen","year":"2023","journal-title":"Front Neurol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.jns.2011.07.028","article-title":"Gerstmann-Str\u00e4ussler-Scheinker syndrome masquerading as multiple sclerosis","volume":"309","author":"Karmon","year":"2011","journal-title":"J Neurol Sci"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1111\/j.1552-6569.2012.00774.x","article-title":"Iodine-123 metaiodobenzylguanidine scintigraphy and iodine-123 ioflupane single photon emission computed tomography in Lewy body diseases: complementary or alternative techniques?","volume":"24","author":"Treglia","year":"2014","journal-title":"J Neuroimaging"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1002\/mdc3.14055","article-title":"I123-FP-CIT (DATSCAN) SPECT beyond the most common causes of parkinsonism: a systematic review","volume":"11","author":"Quintas","year":"2024","journal-title":"Mov Disord Clin Pract"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.2169\/internalmedicine.0573-17","article-title":"Fatal familial insomnia initially developing parkinsonism mimicking dementia with Lewy bodies","volume":"57","author":"Fukuoka","year":"2018","journal-title":"Intern Med"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1002\/mdc3.13385","article-title":"Sporadic fatal insomnia presenting with initial symptoms of parkinsonism and abnormal dopamine transporter imaging","volume":"9","author":"Mkhitarjan","year":"2022","journal-title":"Mov Disord Clin Pract"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"116604","DOI":"10.1016\/j.jns.2019.116604","article-title":"Genetic Creutzfeldt-Jakob disease mimicking dementia with Lewy bodies: clinical and radiological findings","volume":"409","author":"Tomizawa","year":"2020","journal-title":"J Neurol Sci"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1097\/NEN.0b013e3181abdae8","article-title":"The nigrostriatal pathway in Creutzfeldt-Jakob disease","volume":"68","author":"Vital","year":"2009","journal-title":"J Neuropathol Exp Neurol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1016\/j.jocn.2011.11.035","article-title":"Comparison of diffusion-weighted MRI with 18F-fluorodeoxyglucose-positron emission tomography\/CT and electroencephalography in sporadic Creutzfeldt-Jakob disease","volume":"19","author":"Xing","year":"2012","journal-title":"J Clin Neurosci"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"20","DOI":"10.14802\/jmd.19061","article-title":"Progressive Supranuclear palsy with predominant cerebellar ataxia","volume":"13","author":"Ando","year":"2020","journal-title":"J Mov Disord"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"100247","DOI":"10.1016\/j.prdoa.2024.100247","article-title":"Progressive supranuclear palsy phenotype as an atypical clinical presentation of Creutzfeldt-Jakob disease: a case report and review of the literature","volume":"10","author":"Costanzo","year":"2024","journal-title":"Clin Park Relat Disord"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s12915-017-0375-5","article-title":"The biological function of the cellular prion protein: An update","volume":"15","author":"Wulf","year":"2017","journal-title":"BMC Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S1569-2590(08)60182-2","article-title":"Ultrastructural localization of cellular prion protein (PrPc) in synaptic boutons of normal hamster hippocampus","volume":"2","author":"Fournier","year":"1995","journal-title":"CR Acard Sci III Adv Organ Biol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"2464","DOI":"10.1046\/j.1460-9568.1998.00258.x","article-title":"Cellular prion protein localization in rodent and primate brain","volume":"10","author":"Sal\u00e8s","year":"1998","journal-title":"Eur J Neurosci"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.1111\/ejn.12600","article-title":"Cellular prion protein is present in dopaminergic neurons and modulates the dopaminergic system","volume":"40","author":"Rial","year":"2014","journal-title":"Eur J Neurosci"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"8866","DOI":"10.1523\/JNEUROSCI.19-20-08866.1999","article-title":"Evidence of presynaptic location and function of the prion protein","volume":"19","author":"Herms","year":"1999","journal-title":"J Neurosci"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/nature03989","article-title":"The most infectious prion protein particles","volume":"437","author":"Silveira","year":"2005","journal-title":"Nature"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1002\/1097-0029(20000701)50:1<10::AID-JEMT3>3.0.CO;2-6","article-title":"Neuropathology of Gerstmann-Str\u00e4ussler-Scheinker disease","volume":"50","author":"Bugiani","year":"2000","journal-title":"Microsc Res Tech"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.parkreldis.2017.08.012","article-title":"DAT SPECT may have diagnostic value in prodromal SCA2 patients with parkinsonism","volume":"44","author":"Miyaue","year":"2017","journal-title":"Parkinsonism Relat Disord"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1452709\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T04:29:23Z","timestamp":1727065763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1452709\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,23]]},"references-count":43,"alternative-id":["10.3389\/fneur.2024.1452709"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2024.1452709","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,23]]},"article-number":"1452709"}}