{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:04:46Z","timestamp":1791216286615,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,9,29]],"date-time":"2015-09-29T00:00:00Z","timestamp":1443484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>The 42\u2010amino acid fragment of amyloid \u03b2 (A\u03b21\u201042) in cerebrospinal fluid has continued to be important for detecting cerebral \u03b2\u2010amyloidosis in Alzheimer's disease (<jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>). However, there are impediments to our ability to fully understand this measurement, including matrix interference and changes linked to apolipoprotein E (<jats:italic><jats:styled-content style=\"fixed-case\">APOE<\/jats:styled-content><\/jats:italic>) \u03b5<jats:italic>4<\/jats:italic> genotype. This study investigated matrix interference as a contributing factor for detecting <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> in <jats:italic><jats:styled-content style=\"fixed-case\">APOE<\/jats:styled-content><\/jats:italic> \u03b5<jats:italic>4<\/jats:italic>\u2010negative patients by comparing total extractable A\u03b21\u201042 to free A\u03b21\u201042. It also examined the ratio of total A\u03b21\u201042 to A\u03b21\u201040, since changes relative to other A\u03b2 peptides may provide a measurement of cerebral \u03b2\u2010amyloidosis that is neutral to changes in <jats:styled-content style=\"fixed-case\">APP<\/jats:styled-content> metabolism. Total A\u03b21\u201042 lost the diagnostic power for detecting <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>, confirming a role for matrix in the diagnostic. However, when total A\u03b21\u201042\/A\u03b21\u201040 was examined, the separation between groups was reestablished. This result was confirmed in a second sample set of unknown <jats:italic><jats:styled-content style=\"fixed-case\">APOE<\/jats:styled-content><\/jats:italic> status. These results confirmed that matrix interference in some cerebrospinal fluid samples appears to contribute to identifying <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> patients and this can be compensated by using a total extracted A\u03b21\u201042\/A\u03b21\u201040 ratio when matrix interference is small. It may be preferable to employ a total A\u03b21\u201042\/A\u03b21\u201040 measurement, since this could minimize variability because of matrix and compensate for across patient differences.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13297-fig-0004-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nA\u03b21\u201042 measurement in CSF has provided an important tool for early detection of AD. However, it appears that most assays measure a free fraction of A\u03b21\u201042. This study examined total extracted A\u03b21\u201042, since this would provide a more accurate assessment of A\u03b21\u201042 in AD CSF. Total A\u03b21\u201042 measurements alone were not good for detecting AD but total A\u03b21\u201042\/A\u03b21\u201040 performed well.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13297","type":"journal-article","created":{"date-parts":[[2015,9,2]],"date-time":"2015-09-02T19:07:29Z","timestamp":1441220849000},"page":"1049-1058","source":"Crossref","is-referenced-by-count":20,"title":["Impact of cerebrospinal fluid matrix on the detection of Alzheimer's disease with A\u03b242 and influence of disease on the total\u2010A\u03b242\/A\u03b240 ratio"],"prefix":"10.1111","volume":"135","author":[{"given":"J. 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