{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:08:05Z","timestamp":1785211685825,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19AG062418"],"award-info":[{"award-number":["U19AG062418"]}],"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":["R01NS109260"],"award-info":[{"award-number":["R01NS109260"]}],"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\/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"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Adult polyglucosan body disease (APBD) is a progressive neurogenetic disorder caused by 1,4\u2010alpha\u2010glucan branching enzyme 1 (\n                      <jats:italic>GBE1<\/jats:italic>\n                      ) mutation with an accumulation of polyglucosan bodies (PBs) in the central and peripheral nervous systems as a pathological hallmark. Here, we report two siblings in a family with a\n                      <jats:italic>GBE1<\/jats:italic>\n                      mutation with prominent frontotemporal lobar degeneration with TAR DNA\u2010binding protein 43 (FTLD\u2010TDP) and ageing\u2010related tau astrogliopathy (ARTAG) copathologies with PBs in the central nervous system.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Whole\u2010genome sequencing (WGS) followed by Sanger sequencing (SS) was performed on three affected and two unaffected siblings in a pedigree diagnosed with familial frontotemporal dementia. Out of the affected siblings, autopsies were conducted on two cases, and brain samples were used for biochemical and histological analyses. Brain sections were stained with haematoxylin and eosin and immunostained with antibodies against ubiquitin, tau, amyloid \u03b2, \u03b1\u2010synuclein, TDP\u201043 and fused in sarcoma (FUS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A novel single nucleotide deletion in\n                      <jats:italic>GBE1<\/jats:italic>\n                      , c.1280delG, was identified, which is predicted to result in a reading frameshift, p.Gly427Glufs*9. This variant segregated with disease in the family, is absent from population databases and is predicted to cause loss of function, a known genetic mechanism for APBD. The affected siblings showed a greater than 50% decrease in GBE protein levels. Immunohistochemical analysis revealed widespread FTLD\u2010TDP (type A) and ARTAG pathologies as well as PBs in the brains of two affected siblings for whom an autopsy was performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This is the first report of a family with several individuals with a FTD clinical phenotype and underlying copathologies of APBD, FTLD\u2010TDP and ARTAG with a segregating\n                      <jats:italic>GBE1<\/jats:italic>\n                      loss\u2010of\u2010function mutation in affected siblings. The finding of copathologies of APBD and FTLD\u2010TDP suggests these processes may share a disease mechanism resulting from this\n                      <jats:italic>GBE1<\/jats:italic>\n                      mutation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12865","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T02:30:26Z","timestamp":1669948226000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Abundant copathologies of polyglucosan bodies, frontotemporal lobar degeneration with TDP\u201043 inclusions and ageing\u2010related tau astrogliopathy in a family with a\n                    <i>GBE1<\/i>\n                    mutation"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8356-1409","authenticated-orcid":false,"given":"Maiko T.","family":"Uemura","sequence":"first","affiliation":[{"name":"Center for Neurodegenerative Disease Research Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Department of Pathology and Laboratory Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Ran","family":"Suh","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"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 L.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Department of Pathology and Laboratory Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt R.","family":"Brunden","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"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"},{"name":"Penn Frontotemporal Degeneration Center 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"},{"name":"Penn Frontotemporal Degeneration Center Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Penn Digital Neuropathology Laboratory, Department of Neurology Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia M.\u2010Y.","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"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 Q.","family":"Trojanowski","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Research Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Department of Pathology and Laboratory Medicine 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":"Center for Neurodegenerative Disease Research Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Department of Pathology and Laboratory Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Translational Neuropathology Research Laboratory, Department of Pathology and 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