title: Characteristic CSF prion seeding efficiency in humans with prion diseases.
abstract: The development of in vitro amplification systems allows detecting femtomolar amounts of prion protein scrapie (PrP(Sc)) in human cerebrospinal fluid (CSF). We performed a CSF study to determine the effects of prion disease type, codon 129 genotype, PrP(Sc) type, and other disease-related factors on the real-time quaking-induced conversion (RT-QuIC) response. We analyzed times to 10,000 relative fluorescence units, areas under the curve and the signal maximum of RT-QuIC response as seeding parameters of interest. Interestingly, type of prion disease (sporadic vs. genetic) and the PRNP mutation (E200K vs. V210I and FFI), codon 129 genotype, and PrP(Sc) type affected RT-QuIC response. In genetic forms, type of mutation showed the strongest effect on the observed outcome variables. In sporadic CJD, MM1 patients displayed a higher RT-QuIC signal maximum compared to MV1 and VV1. Age and gender were not associated with RT-QuIC signal, but patients with a short disease course showed a higher seeding efficiency of the RT-QuIC response. This study demonstrated that PrP(Sc) characteristics in the CSF of human prion disease patients are associated with disease subtypes and rate of decline as defined by disease duration.
authors.affiliation: Department of Neurology, Clinical Dementia Center, University Medical Center Göttingen and German Center for Neurodegenerative Diseases (DZNE) - site Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Cramm
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmitz
authors.forename: André
authors.initials: A
authors.lastname: Karch
authors.forename: Saima
authors.initials: S
authors.lastname: Zafar
authors.forename: Daniela
authors.initials: D
authors.lastname: Varges
authors.forename: Eva
authors.initials: E
authors.lastname: Mitrova
authors.forename: Bjoern
authors.initials: B
authors.lastname: Schroeder
authors.forename: Alex
authors.initials: A
authors.lastname: Raeber
authors.forename: Franziska
authors.initials: F
authors.lastname: Kuhn
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D003062:Codon / Q000235:genetics; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000473:pathology; D016643:Encephalopathy, Bovine Spongiform / Q000235:genetics / Q000473:pathology; D023381:Endpoint Determination; D005260:Female; D005838:Genotype; D006801:Humans; D034062:Insomnia, Fatal Familial / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D017096:Prion Diseases / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000473:pathology*; D011328:Prions / Q000134:cerebrospinal fluid*; D013129:Spinal Puncture; D013997:Time Factors; D055815:Young Adult
chemical_list: D003062:Codon; D011328:Prions