title: Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease.
abstract: Human prion diseases are infectious and invariably fatal neurodegenerative diseases. They include sporadic Creutzfeldt-Jakob disease (sCJD), the most common form, and variant CJD (vCJD), which is caused by interspecies transmission of prions from cattle infected by bovine spongiform encephalopathy. Development of a biochemical assay for the sensitive, specific, early, and noninvasive detection of prions (PrPSc) in the blood of patients affected by prion disease is a top medical priority to increase the safety of the blood supply. vCJD has already been transmitted from human to human by blood transfusion, and the number of asymptomatic carriers of vCJD in the U.K. alone is estimated to be 1 in 2000 people. We used the protein misfolding cyclic amplification (PMCA) technique to analyze blood samples from 14 cases of vCJD and 153 controls, including patients affected by sCJD and other neurodegenerative or neurological disorders as well as healthy subjects. Our results showed that PrPSccould be detected with 100% sensitivity and specificity in blood samples from vCJD patients. Detection was possible in any of the blood fractions analyzed and could be done with as little as a few microliters of sample volume. The PrPScconcentration in blood was estimated to be ~0.5 pg/ml. Our findings suggest that PMCA may be useful for premortem noninvasive diagnosis of vCJD and to identify prion contamination of the blood supply. Further studies are needed to fully validate the technology.
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas Houston Medical School, Houston, TX 77030, USA.|Universidad de los Andes, Facultad de Medicina, Avenida San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Concha-Marambio
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas Houston Medical School, Houston, TX 77030, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pritzkow
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas Houston Medical School, Houston, TX 77030, USA.|IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Moda
authors.affiliation: IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
authors.affiliation: National CJD Research and Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, U.K.
authors.forename: James W
authors.initials: JW
authors.lastname: Ironside
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas Houston Medical School, Houston, TX 77030, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Schulz
authors.affiliation: Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas Houston Medical School, Houston, TX 77030, USA. claudio.soto@uth.tmc.edu.|Universidad de los Andes, Facultad de Medicina, Avenida San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile.
authors.forename: Claudio
authors.initials: C
authors.lastname: Soto
mesh_terms: D016022:Case-Control Studies; D007562:Creutzfeldt-Jakob Syndrome / Q000097:blood* / Q000175:diagnosis*; D006403:Hematologic Tests / Q000379:methods*; D006801:Humans; D007558:Italy; D011328:Prions / Q000097:blood*; D012680:Sensitivity and Specificity; D006113:United Kingdom
chemical_list: D011328:Prions