{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:46:16Z","timestamp":1791200776830,"version":"4.2.0"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,11,28]],"date-time":"2011-11-28T00:00:00Z","timestamp":1322438400000},"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":[[2012,1]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:italic>J. Neurochem.<\/jats:italic> (2012) <jats:bold>120<\/jats:bold>, 325\u2013333.<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>A\u03b21\u201342 measurement in CSF is an important biochemical marker for Alzheimer disease (AD). However, our understanding of why this biomarker is predictive and why it is often difficult to measure in a reproducible fashion is still lacking. To study these questions, the concentration of A\u03b21\u201342 in CSF was compared before and after denaturation with 6M guanidine and reverse\u2010phase HPLC. Measurement of the A\u03b21\u201342 after denaturation and reverse\u2010phase HPLC demonstrated that considerably more A\u03b21\u201342 was present in CSF than revealed when assaying non\u2010denatured CSF. A comparison of A\u03b21\u201342 concentrations before and after HPLC in AD CSF with that in normal controls suggested that matrix interference may affect the differentiation between the diagnostic groups. A similar effect was observed with dilutions of crude CSF. Together, these results suggested that at least part of the mechanism by which low A\u03b21\u201342 concentrations in CSF function as a biomarker of AD is related to matrix components which preferentially hide a portion of the A\u03b21\u201342 from detection in AD CSF. In contrast, we show that the association of the <jats:italic>APOE<\/jats:italic>\u03b54 allele with lower A\u03b21\u201342 concentrations in CSF is preserved even after denaturation and HPLC. A similar relationship between the presence of the <jats:italic>APOE<\/jats:italic>\u03b54 allele and lower concentrations of A\u03b21\u201340 was also apparent, thereby generating similar ratios of A\u03b21\u201342\/ A\u03b21\u201340 across the <jats:italic>APOE<\/jats:italic> genotypes. The results from the present study suggested that A\u03b21\u201342 in CSF functions as a biomarker of AD in tandem with other CSF matrix components that are increased in AD CSF. Further studies are needed to identify which matrix factors (e.g. binding of A\u03b2 to proteins) underlie the increased detection of A\u03b21\u201342 concentrations after denaturation and HPLC. The data also suggested that denaturation and HPLC of CSF may be a useful approach for studies using A\u03b21\u201342 as a pharmacodynamic marker or in other paradigms where measurement of total non\u2010covalently bound A\u03b21\u201342 is required.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1471-4159.2011.07553.x","type":"journal-article","created":{"date-parts":[[2011,10,25]],"date-time":"2011-10-25T07:32:28Z","timestamp":1319527948000},"page":"325-333","source":"Crossref","is-referenced-by-count":33,"title":["Measurement of A\u03b21\u201342 in cerebrospinal fluid is influenced by matrix effects"],"prefix":"10.1111","volume":"120","author":[{"given":"J. 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