{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:44:24Z","timestamp":1790693064438,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,5,27]],"date-time":"2013-05-27T00:00:00Z","timestamp":1369612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:p><jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>iemann\u2010<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>ick disease type <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>) is an autosomal recessive neurovisceral lipid storage disorder. Two disease\u2010causing genes (<jats:italic><jats:styled-content style=\"fixed-case\">NPC1<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">NPC2<\/jats:styled-content><\/jats:italic>) have been identified. <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content> is characterized by neuronal and glial lipid storage and <jats:styled-content style=\"fixed-case\">NFTs<\/jats:styled-content>. Here, we report a man with juvenile\u2010onset progressive neurological deficits, including pyramidal signs, ataxia, bulbar palsy, vertical supranuclear ophthalmoplegia, and psychiatric symptoms; death occurred at age 37 before definitive clinical diagnosis. Post mortem gross examination revealed a unique distribution of brain atrophy, predominantly in the frontal and temporal lobes. Microscopically, lipid storage in neurons and widely distributed <jats:styled-content style=\"fixed-case\">NFTs<\/jats:styled-content> were observed. Lipid storage cells appeared in systemic organs and filipin staining indicated intracellular cholesterol accumulation in hepatic macrophages. Electron microscopy revealed accumulation of lipids and characteristic oligolamellar inclusions. These findings suggested an <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content> diagnosis. Neuronal loss and gliosis were frequently accompanied by <jats:styled-content style=\"fixed-case\">NFTs<\/jats:styled-content> and occurred in the frontal and temporal cortices, hippocampus, amygdala, basal forebrain, basal ganglia, thalamus, substantia nigra and brain stem nuclei. Lewy bodies (<jats:styled-content style=\"fixed-case\">LBs<\/jats:styled-content>) were observed in most, but not all, regions where <jats:styled-content style=\"fixed-case\">NFTs<\/jats:styled-content> were evident. In contrast, neuronal lipid storage occurred in more widespread areas, including the parietal and occipital cortices where neurodegeneration with either <jats:styled-content style=\"fixed-case\">NFTs<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">LBs<\/jats:styled-content> was minimal. Molecular genetic analysis demonstrated that the patient had compound heterozygous mutations in the cysteine\u2010rich loop (<jats:styled-content style=\"fixed-case\">A1017T<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">Y1088C<\/jats:styled-content>) of the <jats:italic><jats:styled-content style=\"fixed-case\">NPC1<\/jats:styled-content><\/jats:italic> gene. To our knowledge there has been no previous report of the A1017T mutation. The pathological features of this patient support the notion that <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content> has an aspect of \u03b1\u2010synucleinopathy, and long\u2010term survivors of <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content> may develop a frontotemporal\u2010predominant distribution of brain atrophy.<\/jats:p>","DOI":"10.1111\/neup.12047","type":"journal-article","created":{"date-parts":[[2013,5,27]],"date-time":"2013-05-27T07:54:50Z","timestamp":1369641290000},"page":"49-57","source":"Crossref","is-referenced-by-count":44,"title":["Niemann\u2010<scp>P<\/scp>ick disease type <scp>C<\/scp>1 predominantly involving the frontotemporal region, with cortical and brainstem <scp>L<\/scp>ewy bodies: An autopsy case"],"prefix":"10.1111","volume":"34","author":[{"given":"Yoichi","family":"Chiba","sequence":"first","affiliation":[{"name":"Department of Pathology Institute for Developmental Research Aichi Human Service Center  Kasugai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiraku","family":"Komori","sequence":"additional","affiliation":[{"name":"Kobato Gakuen Aichi Human Service Center  Kasugai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Takei","sequence":"additional","affiliation":[{"name":"Department of Pathology Institute for Developmental Research Aichi Human Service Center  Kasugai Japan"},{"name":"Faculty of Nutrition Koshien University  Takarazuka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanae","family":"Hasegawa\u2010Ishii","sequence":"additional","affiliation":[{"name":"Department of Pathology Institute for Developmental Research Aichi Human Service Center  Kasugai Japan"},{"name":"Japan Society for the Promotion of Science  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Pathology Institute for Developmental Research Aichi Human Service Center  Kasugai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Adachi","sequence":"additional","affiliation":[{"name":"Division of Functional Genomics Research Center for Bioscience and Technology Tottori University  Yonago Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Nanba","sequence":"additional","affiliation":[{"name":"Division of Functional Genomics Research Center for Bioscience and Technology Tottori University  Yonago Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Hosokawa","sequence":"additional","affiliation":[{"name":"Department of Pathology Institute for Developmental Research Aichi Human Service Center  Kasugai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Enokido","sequence":"additional","affiliation":[{"name":"Department of Pathology Institute for Developmental Research Aichi Human Service Center  Kasugai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zen","family":"Kouchi","sequence":"additional","affiliation":[{"name":"Department of Pathology Institute for Developmental Research Aichi Human Service Center  Kasugai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Futoshi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Central Hospital, Aichi Human Service Center  Kasugai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuyoshi","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Pathology Institute for Developmental Research Aichi Human Service Center  Kasugai Japan"},{"name":"Department of Pathology and Laboratory Medicine and Radiologic Technology Central Hospital, Aichi Human Service Center  Kasugai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,5,27]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"3611","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Patterson MC","year":"2001"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-16"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00309338"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/118.1.119"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl260"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/63.4.323"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.05.024"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1679\/aohc.70.43"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2012.01.026"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00939-5"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200107200-00009"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0384-7"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.74.4.528"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.2006.18.2.158"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2010.08.004"},{"key":"e_1_2_6_17_1","first-page":"293","article-title":"Adult onset Niemann\u2010Pick disease type C presenting with dementia and absent organomegaly","volume":"11","author":"Hulette CM","year":"1992","journal-title":"Clin Neuropathol"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10366"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181e6210e"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1082324"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-009-9190-y"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199812000-00011"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.04.011"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0264-z"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.01220.x"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00531-1"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00690966"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022575511354"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/60.1.49"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390051057"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1086\/301931"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.4976"}],"container-title":["Neuropathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fneup.12047","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/neup.12047","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T02:20:13Z","timestamp":1696472413000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/neup.12047"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,27]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,2]]}},"alternative-id":["10.1111\/neup.12047"],"URL":"https:\/\/doi.org\/10.1111\/neup.12047","archive":["Portico"],"relation":{},"ISSN":["0919-6544","1440-1789"],"issn-type":[{"value":"0919-6544","type":"print"},{"value":"1440-1789","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,27]]}}}