{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:27:47Z","timestamp":1791556067171,"version":"4.3.4"},"reference-count":66,"publisher":"National Academy of Sciences","issue":"30","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,7,25]]},"abstract":"<jats:p>\n                    Prions are composed solely of an alternatively folded isoform of the prion protein (PrP), designated PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    . The polyoxometalate phosphotungstic acid has been used to separate PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    from its precursor PrP\n                    <jats:sup>C<\/jats:sup>\n                    by selective precipitation; notably, native PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    has not been solubilized by using nondenaturing detergents. Because of the similarities between PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    and lipoproteins with respect to hydrophobicity and formation of phosphotungstic acid complexes, we asked whether these molecules are bound to each other in blood. Here we report that prions from the brains of patients with sporadic Creutzfeldt\u2013Jakob disease (CJD) bind to very low-density (VLDL) and low-density (LDL) lipoproteins but not to high-density lipoproteins (HDL) or other plasma components, as demonstrated both by affinity assay and electron microscopy. Immunoassays demonstrated that apolipoprotein B (apoB), which is the major protein component of VLDL and LDL, bound PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    through a highly cooperative process. Approximately 50% of the PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    bound to LDL particles was released after exposure to 4 M guanidine hydrochloride at 80\u00b0C for 20 min. The apparent binding constants of native human (Hu) PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    or denatured recombinant HuPrP(90\u2013231) for apoB and LDL ranged from 28 to 212 pM. Whether detection of PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    in VLDL and LDL particles can be adapted into an antemortem diagnostic test for prions in the blood of humans, livestock, and free-ranging cervids remains to be determined.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0604021103","type":"journal-article","created":{"date-parts":[[2006,7,18]],"date-time":"2006-07-18T20:35:07Z","timestamp":1153254907000},"page":"11312-11317","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":42,"title":["Human prions and plasma lipoproteins"],"prefix":"10.1073","volume":"103","author":[{"given":"Jiri G.","family":"Safar","sequence":"first","affiliation":[{"name":"*Institute for Neurodegenerative Diseases,"},{"name":"Departments of \u2020Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Wille","sequence":"additional","affiliation":[{"name":"*Institute for Neurodegenerative Diseases,"},{"name":"Departments of \u2020Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Geschwind","sequence":"additional","affiliation":[{"name":"Departments of \u2020Neurology,"},{"name":"Memory and Aging Center, University of California, San Francisco, CA 94143; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Deering","sequence":"additional","affiliation":[{"name":"*Institute for Neurodegenerative Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Latawiec","sequence":"additional","affiliation":[{"name":"*Institute for Neurodegenerative Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Serban","sequence":"additional","affiliation":[{"name":"*Institute for Neurodegenerative Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"King","sequence":"additional","affiliation":[{"name":"*Institute for Neurodegenerative Diseases,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Legname","sequence":"additional","affiliation":[{"name":"*Institute for Neurodegenerative Diseases,"},{"name":"Departments of \u2020Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl H.","family":"Weisgraber","sequence":"additional","affiliation":[{"name":"Gladstone Institute, University of California, San Francisco, CA 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Mahley","sequence":"additional","affiliation":[{"name":"Gladstone Institute, University of California, San Francisco, CA 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce L.","family":"Miller","sequence":"additional","affiliation":[{"name":"Departments of \u2020Neurology,"},{"name":"Memory and Aging Center, University of California, San Francisco, CA 94143; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"DeArmond","sequence":"additional","affiliation":[{"name":"*Institute for Neurodegenerative Diseases,"},{"name":"Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley B.","family":"Prusiner","sequence":"additional","affiliation":[{"name":"*Institute for Neurodegenerative Diseases,"},{"name":"Departments of \u2020Neurology,"},{"name":"Biochemistry and Biophysics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,7,25]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(84)90533-6"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.12.4017"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/2654"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-662-12004-0"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja055219y"},{"key":"e_1_3_4_6_2","first-page":"1","volume-title":"Monographs on Atherosclerosis","author":"Burstein M.","year":"1982","unstructured":"M. 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