{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:26:21Z","timestamp":1792002381208,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Quaking\u2010induced conversion (QuIC) tests, which detect prion\u2010seeding activity in cerebrospinal fluid (CSF), have markedly advanced the antemortem diagnosis of prion diseases such as Creutzfeldt\u2010Jakob disease (CJD). These tests provide high diagnostic accuracy and enable timely differentiation from other rapidly progressive neurodegenerative disorders. However, a key limitation of current QuIC tests are the reduced sensitivity in detecting inherited prion diseases and rare sporadic subtypes, including variably protease\u2010sensitive prionopathy (VPSPr). To address this gap, we evaluated a simplified QuIC test, end\u2010point QuIC (EP\u2010QuIC), incorporating a novel recombinant prion protein substrate derived from the North American deer mouse (\n                      <jats:italic>Peromyscus maniculatus<\/jats:italic>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The diagnostic performance of the modified QuIC test was evaluated using CSF samples from 61 sporadic CJD, 50 inherited prion disease, and 5 VPSPr cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>EP\u2010QuIC with the deer mouse substrate achieved 96.6% sensitivity (111\/116) and 100% specificity (35\/35), outperforming both standard EP\u2010QuIC (87.1%) and next\u2010generation (IQ\u2010CSF) real\u2010time\u2010QuIC (72.4%) across the same cohort. Notably, this enhanced assay detected inherited mutations, such as D178N, that were previously undetectable with existing diagnostic tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>These findings demonstrate that adapting EP\u2010QuIC with an optimized substrate, termed enhanced sensitivity QuIC (ES\u2010QuIC), significantly improves diagnostic performance for inherited and atypical prion diseases. By expanding the diagnostic reach of QuIC tests, this study strengthens antemortem surveillance, reduces reliance on postmortem confirmation, and improves opportunities for early intervention and clinical trial enrollment, particularly for genetic cases most likely to benefit from emerging therapeutic strategies. ANN NEUROL 2026;99:1303\u20131314<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78162","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T12:42:01Z","timestamp":1769431321000},"page":"1303-1314","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Enhanced Sensitivity of a Modified Quaking\u2010Induced Conversion Diagnostic Test for the Broad Detection of Sporadic and Inherited Prion Diseases: A Retrospective Study"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0625-7130","authenticated-orcid":false,"given":"Jennifer","family":"Myskiw","sequence":"first","affiliation":[{"name":"Mycobacteriology, Vector\u2010borne and Prion Diseases Division, National Microbiology Laboratory, Public Health Agency of Canada  Winnipeg MB 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