{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T11:15:18Z","timestamp":1778843718850,"version":"3.51.4"},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15K15083"],"award-info":[{"award-number":["15K15083"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI 26242085"],"award-info":[{"award-number":["KAKENHI 26242085"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disord Clin Pract"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>MAPT<\/jats:italic>\n                      is a causative gene in frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP\u201017), a hereditary degenerative disease with various clinical manifestations, including progressive supranuclear palsy, corticobasal syndrome, Parkinson's disease, and frontotemporal dementia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To analyze genetically, biochemically, and pathologically multiple members of two families who exhibited various phenotypes of the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Genetic analysis included linkage analysis, homozygosity haplotyping, and exome sequencing. We conducted tau protein microtubule polymerization assay, heparin\u2010induced tau aggregation, and western blotting with brain lysate from an autopsy case. We also evaluated abnormal tau aggregation by using anti\u2010tau antibody and PM\u2010PBB3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a variant, c.896_897insACA, p.K298_H299insQ, in the\n                      <jats:italic>MAPT<\/jats:italic>\n                      gene of affected patients. Similar to previous reports, most patients presented with atypical parkinsonism. Biochemical analysis revealed that the mutant tau protein had a reduced ability to polymerize microtubules and formed abnormal fibrous aggregates. Pathological study revealed frontotemporal lobe atrophy, midbrain atrophy, depigmentation of the substantia nigra, and four\u2010repeat tau\u2010positive inclusions in the hippocampus, brainstem, and spinal cord neurons. The inclusion bodies also stained positively with PM\u2010PBB3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study confirmed that the insACA mutation caused FTDP\u201017. The affected patients showed symptoms resembling Parkinson's disease initially and symptoms of progressive supranuclear palsy later. Despite the initial clinical diagnosis of frontotemporal dementia in the autopsy case, the spread of lesions could explain the process of progressive supranuclear palsy. The study of more cases in the future will help clarify the common pathogenesis of\n                      <jats:italic>MAPT<\/jats:italic>\n                      mutations or specific pathogeneses of each mutation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mdc3.14042","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T02:25:25Z","timestamp":1712888725000},"page":"720-727","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical and Pathological Features of\n                    <scp>FTDP<\/scp>\n                    \u201017 with\n                    <scp>\n                      <i>MAPT<\/i>\n                    <\/scp>\n                    p.K298_H299insQ Mutation"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5190-3547","authenticated-orcid":false,"given":"Hiroyuki","family":"Morino","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Tokushima University Graduate School of Biomedical Sciences  Tokushima Japan"},{"name":"Department of Molecular Epidemiology, Research Institute for Radiation Biology and Medicine Hiroshima University  Hiroshima Japan"},{"name":"Department of Clinical Neuroscience &amp; Therapeutics, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5206-5979","authenticated-orcid":false,"given":"Takashi","family":"Kurashige","sequence":"additional","affiliation":[{"name":"Department of Neurology National Hospital Organization Kure Medical Center and Chugoku Cancer Center  Kure Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6213-7745","authenticated-orcid":false,"given":"Yukiko","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Molecular Epidemiology, Research Institute for Radiation Biology and Medicine Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maiko","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Functional Brain Imaging, Institute for Quantum Medical Science National Institutes for Quantum Science and Technology  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2122-5797","authenticated-orcid":false,"given":"Naruhiko","family":"Sahara","sequence":"additional","affiliation":[{"name":"Department of Functional Brain Imaging, Institute for Quantum Medical Science National Institutes for Quantum Science and Technology  Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4867-7910","authenticated-orcid":false,"given":"Tomohiro","family":"Miyasaka","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Faculty of Life and Medical Sciences Doshisha University  Kyotanabe Japan"},{"name":"Laboratory of Physiology &amp; Anatomy Nihon University School of Pharmacy  Funabashi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9657-4102","authenticated-orcid":false,"given":"Yoshiyuki","family":"Soeda","sequence":"additional","affiliation":[{"name":"Faculty of Science Gakushuin University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7139-7178","authenticated-orcid":false,"given":"Hitoshi","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Functional Brain Imaging, Institute for Quantum Medical Science National Institutes for Quantum Science and Technology  Chiba Japan"},{"name":"Department of Functional Neurology &amp; Neurosurgery, Center for Integrated Human Brain Science, Brain Research Institute Niigata University  Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0806-4960","authenticated-orcid":false,"given":"Yu","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience &amp; Therapeutics, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6891-0842","authenticated-orcid":false,"given":"Tetsuya","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience &amp; Therapeutics, Graduate School of Biomedical and Health Sciences Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3048-9041","authenticated-orcid":false,"given":"Yuishin","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience Tokushima University Graduate School of Biomedical Sciences  Tokushima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidefumi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Neurology Wakayama Medical University  Wakayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7613-8717","authenticated-orcid":false,"given":"Hirofumi","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience &amp; 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