{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:59:05Z","timestamp":1791410345076,"version":"4.3.3"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,1,24]],"date-time":"2017-01-24T00:00:00Z","timestamp":1485216000000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["UR8\/CCU515004"],"award-info":[{"award-number":["UR8\/CCU515004"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS074317"],"award-info":[{"award-number":["NS074317"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Several prion amplification systems have been proposed for detection of prions in cerebrospinal fluid (CSF), most recently, the measurements of prion seeding activity with second\u2010generation real\u2010time quaking\u2010induced conversion (RT\u2010QuIC). The objective of this study was to investigate the diagnostic performance of the RT\u2010QuIC prion test in the broad phenotypic spectrum of prion diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed CSF RT\u2010QuIC testing in 2,141 patients who had rapidly progressive neurological disorders, determined diagnostic sensitivity and specificity in 272 cases that were autopsied, and evaluated the impact of mutations and polymorphisms in the <jats:italic>PRNP<\/jats:italic> gene, and type 1 or type 2 human prions on diagnostic performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The 98.5% diagnostic specificity and 92% sensitivity of CSF RT\u2010QuIC in a blinded retrospective analysis matched the 100% specificity and 95% sensitivity of a blind prospective study. The CSF RT\u2010QuIC differentiated 94% of cases of sporadic Creutzfeldt\u2013Jakob disease (sCJD) MM1 from the sCJD MM2 phenotype, and 80% of sCJD VV2 from sCJD VV1. The mixed prion type 1\u20102 and cases heterozygous for codon 129 generated intermediate CSF RT\u2010QuIC patterns, whereas genetic prion diseases revealed distinct profiles for each <jats:italic>PRNP<\/jats:italic> gene mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The diagnostic performance of the improved CSF RT\u2010QuIC is superior to surrogate marker tests for prion diseases such as 14\u20103\u20103 and tau proteins, and together with <jats:italic>PRNP<\/jats:italic> gene sequencing the test allows the major prion subtypes to be differentiated in vivo. This differentiation facilitates prediction of the clinicopathological phenotype and duration of the disease\u2014two important considerations for envisioned therapeutic interventions. 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