{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:33:20Z","timestamp":1789875200637,"version":"4.0.1"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,5,9]]},"abstract":"<jats:p>\n                    A definite diagnosis of prion diseases such as Creutzfeldt\u2013Jakob disease (CJD) relies on the detection of pathological prion protein (PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    ). However, no test for PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    in cerebrospinal fluid (CSF) has been available thus far. Based on a setup for confocal dual-color fluorescence correlation spectroscopy, a technique suitable for single molecule detection, we developed a highly sensitive detection method for PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    . Pathological prion protein aggregates were labeled by specific antibody probes tagged with fluorescent dyes, resulting in intensely fluorescent targets, which were measured by dual-color fluorescence intensity distribution analysis in a confocal scanning setup. In a diagnostic model system, PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    aggregates were detected down to a concentration of 2 pM PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    , corresponding to an aggregate concentration of approximately 2 fM, which was more than one order of magnitude more sensitive than Western blot analysis. A PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    -specific signal could also be detected in a number of CSF samples from patients with CJD but not in control samples, providing the basis for a rapid and specific test for CJD and other prion diseases. Furthermore, this method could be adapted to the sensitive detection of other disease-associated amyloid aggregates such as in Alzheimer's disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.97.10.5468","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:38:21Z","timestamp":1027679901000},"page":"5468-5473","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":192,"title":["Ultrasensitive detection of pathological prion protein aggregates by dual-color scanning for intensely fluorescent targets"],"prefix":"10.1073","volume":"97","author":[{"given":"J.","family":"Bieschke","sequence":"first","affiliation":[{"name":"Max-Planck-Institute for Biophysical Chemistry, Am Fassberg, 37077 G\u00f6ttingen, Germany; and Departments of Neuropathology and Neurology,  University of G\u00f6ttingen, Robert-Koch-Strasse 40, 37075 G\u00f6ttingen, 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