{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:30:01Z","timestamp":1777397401142,"version":"3.51.4"},"reference-count":27,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["UK Medical Research Council Award to the MRC Prion"],"award-info":[{"award-number":["UK Medical Research Council Award to the MRC Prion"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR Biomedical Research Centre","award":["Clinical Research Activities are supported by Nati"],"award-info":[{"award-number":["Clinical Research Activities are supported by Nati"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      PrP systemic amyloidosis is increasingly recognized as a novel inherited prion disease (IPD) syndrome caused by\n                      <jats:italic toggle=\"yes\">PRNP<\/jats:italic>\n                      C-terminal truncating mutations. As well as systemic manifestations they cause gradually progressive cognitive impairment with neurofibrillary tangle pathology which can be mistaken for Alzheimer's disease (AD).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      We describe the clinical, biomarker and neuropathological features of a novel frameshift mutation of\n                      <jats:italic toggle=\"yes\">PRNP<\/jats:italic>\n                      resulting in protein truncation at codon 157.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The clinical phenotype and biomarker findings, including plasma biomarkers measured using Single Molecule Array (SiMOA) technology are reported for affected living individuals, with neuropathological examination available for the index case.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The Y157X\n                      <jats:italic toggle=\"yes\">PRNP<\/jats:italic>\n                      mutation has resulted in a phenotype of gradually progressive cognitive decline, peripheral sensory and autonomic polyneuropathy, and gastrointestinal symptoms, with one case presenting with recurrent episodes of nausea, vomiting and electrolyte derangement requiring intensive care unit admission. Plasma biomarkers revealed an AD-like pattern with raised neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and phospho-tau 181 (P-tau 181) in affected individuals. On neuropathological examination there was PrP-cerebral amyloid angiopathy (CAA) and neurofibrillary tau pathology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We present the clinical, biomarker and pathological findings on investigation of this family and provide further evidence for the association of truncation mutations with PrP systemic amyloidosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251351182","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T03:23:26Z","timestamp":1751599406000},"page":"1087-1096","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Inherited prion disease caused by a novel frameshift mutation of\n                    <i>PRNP<\/i>\n                    resulting in protein truncation at codon 157"],"prefix":"10.1177","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5723-3310","authenticated-orcid":false,"given":"Leah","family":"Holm-Mercer","sequence":"first","affiliation":[{"name":"MRC Prion Unit at UCL, UCL Institute of Prion Diseases, University College London, London, UK"},{"name":"NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tze How","family":"Mok","sequence":"additional","affiliation":[{"name":"MRC Prion Unit at UCL, UCL Institute of Prion Diseases, University College London, London, UK"},{"name":"NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9427-9320","authenticated-orcid":false,"given":"Danielle","family":"Sequeira","sequence":"additional","affiliation":[{"name":"MRC Prion Unit at UCL, UCL Institute of Prion Diseases, University College London, London, UK"},{"name":"NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9928-4039","authenticated-orcid":false,"given":"Thomas","family":"Coysh","sequence":"additional","affiliation":[{"name":"MRC Prion Unit at UCL, UCL Institute of Prion Diseases, University College London, London, UK"},{"name":"NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Rudge","sequence":"additional","affiliation":[{"name":"MRC Prion Unit at UCL, UCL Institute of Prion Diseases, University College London, London, UK"},{"name":"NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hawraman","family":"Ramadan","sequence":"additional","affiliation":[{"name":"Bradford Teaching Hospitals NHS Foundation Trust"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee","family":"Darwent","sequence":"additional","affiliation":[{"name":"MRC Prion Unit at UCL, UCL Institute of Prion Diseases, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy","family":"Campbell","sequence":"additional","affiliation":[{"name":"MRC Prion Unit at UCL, UCL Institute of Prion Diseases, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Murphy","sequence":"additional","affiliation":[{"name":"MRC Prion Unit at UCL, UCL Institute of Prion Diseases, University College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin","family":"Smith","sequence":"additional","affiliation":[{"name":"Academic Department of Neuropathology, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Academic Department of Neuropathology, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Brandner","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology"},{"name":"Division of Neuropathology, National Hospital for Neurology and Neurosurgery, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zane","family":"Jaunmuktane","sequence":"additional","affiliation":[{"name":"Division of Neuropathology, National Hospital for Neurology and Neurosurgery, London, UK"},{"name":"UCL Queen Square Institute of Neurology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Collinge","sequence":"additional","affiliation":[{"name":"MRC Prion Unit at UCL, UCL Institute of Prion Diseases, University College London, London, UK"},{"name":"NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Mead","sequence":"additional","affiliation":[{"name":"MRC Prion Unit at UCL, UCL Institute of Prion Diseases, University College London, London, UK"},{"name":"NHS 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