{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:33:03Z","timestamp":1791952383593,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RF1AG065341"],"award-info":[{"award-number":["RF1AG065341"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R56AG063344"],"award-info":[{"award-number":["R56AG063344"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30AG072979"],"award-info":[{"award-number":["P30AG072979"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01AG066597"],"award-info":[{"award-number":["P01AG066597"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000862","name":"Doris Duke Charitable Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000862","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      The clinical, radiological, and pathological features have not been well documented for the recently discovered autosomal\u2010dominant vacuolar tauopathy (VT) harboring the Valosin\u2010containing protein (\n                      <jats:italic>VCP)<\/jats:italic>\n                      p.Asp395Gly variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We investigated the clinical, neuropsychological, physiological, laboratory, and radiological data and neuropathological findings in five symptomatic VT cases who met the diagnostic criteria for frontotemporal dementia (FTD). Radiological data were also collected from two pre\u2010symptomatic carriers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      All participants had heterozygous c.1184A\u00a0&gt;\u00a0G, p.Asp395Gly in\n                      <jats:italic>VCP<\/jats:italic>\n                      . All symptomatic cases exhibited cognitive, behavioral, and\/or language dysfunction indicative of FTD in their 30s to 50s. Neuroimaging studies revealed marked bilateral frontal neurodegeneration and occipital lobar diffusion abnormalities. Post mortem examination of three cases and brain biopsy of one case revealed abundant three\u2010 and four\u2010repeat tau deposition and neocortical microvacuolization. Radiological changes were not evident in two pre\u2010symptomatic carriers in their 20s.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>This study reveals distinct clinical\u2010radiological\u2010pathological correlations in VT, expanding the spectrum of early\u2010onset frontotemporal lobar degeneration (FTLD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>We characterized the clinical, radiological, and pathological features of vacuolar tauopathy (VT).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Five VT cases exhibited a behavioral syndrome, often with aphasic features, with marked frontal lobar atrophy and hypometabolism.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Magnetic resonance imaging (MRI) of VT cases revealed occipital lobar diffusion abnormalities.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Diffuse neurofibrillary tangles (NFTs) and microvacuolization were observed in the neocortex, with an inverse distribution.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70427","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T08:40:03Z","timestamp":1752828003000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinicopathological characterization of vacuolar tauopathy associated with\n                    <i>VCP<\/i>\n                    D395G"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0775-656X","authenticated-orcid":false,"given":"Ryohei","family":"Watanabe","sequence":"first","affiliation":[{"name":"Translational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Papatriantafyllou","sequence":"additional","affiliation":[{"name":"Medical Center of Athens, Memory Disorders Clinic and Day Care Center for 3rd Age \u2018IASIS\u2019  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kengo","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Neurology Vories Memorial Hospital  Omihachiman Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey K.","family":"Aguirre","sequence":"additional","affiliation":[{"name":"Department of Neurology Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University, Graduate School of Medical and Dental Sciences  Sakuragaoka Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernice","family":"Benoit","sequence":"additional","affiliation":[{"name":"Translational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray","family":"Grossman","sequence":"additional","affiliation":[{"name":"Department of Neurology Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Irwin","sequence":"additional","affiliation":[{"name":"Department of Neurology Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boram","family":"Kim","sequence":"additional","affiliation":[{"name":"Translational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Massimo","sequence":"additional","affiliation":[{"name":"Department of Neurology Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey T.","family":"McMillan","sequence":"additional","affiliation":[{"name":"Department of Neurology Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sokratis G.","family":"Papageorgiou","sequence":"additional","affiliation":[{"name":"1st University Department of Neurology, Eginiteio University Hospital, National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Neurology Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Higashi\u2010ohmi General Medical Center  Higashi\u2010ohmi Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Sugihara","sequence":"additional","affiliation":[{"name":"Department of Neurology JCHO Shiga Hospital  Otsu Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EunRan","family":"Suh","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Takashima","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University, Graduate School of Medical and Dental Sciences  Sakuragaoka Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo","family":"Toro","sequence":"additional","affiliation":[{"name":"NIH Undiagnosed Diseases Program, National Human Genome Research Institute  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivianna M.","family":"Van Deerlin","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya M.","family":"Nasrallah","sequence":"additional","affiliation":[{"name":"Department of Radiology Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward B.","family":"Lee","sequence":"additional","affiliation":[{"name":"Translational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania 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&amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70427","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.70427","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70427","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:58:50Z","timestamp":1784303930000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":24,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/alz.70427"],"URL":"https:\/\/doi.org\/10.1002\/alz.70427","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2025-02-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70427"}}