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This study aimed to determine whether CSF<\/jats:styled-content> A\u03b2<\/jats:italic>42\/A\u03b2<\/jats:italic>40 and A\u03b2<\/jats:italic>42\/A\u03b2<\/jats:italic>38 ratios are better diagnostic biomarkers of AD<\/jats:styled-content> during both predementia and dementia stages in comparison to CSF<\/jats:styled-content> A\u03b2<\/jats:italic>42 alone.<\/jats:p><\/jats:sec>Methods<\/jats:title>The study comprised three different cohorts (n<\/jats:italic> = 1182) in whom CSF<\/jats:styled-content> levels of A\u03b2<\/jats:italic>42, A\u03b2<\/jats:italic>40, and A\u03b2<\/jats:italic>38 were assessed. CSF<\/jats:styled-content> A\u03b2<\/jats:italic>s were quantified using three different immunoassays (Euroimmun, Meso Scale Discovery, Quanterix). As reference standard, we used either amyloid (18<\/jats:sup>F\u2010flutemetamol) positron emission tomography (PET<\/jats:styled-content>) imaging (n<\/jats:italic> = 215) or clinical diagnosis (n<\/jats:italic> = 967) of well\u2010characterized patients.<\/jats:p><\/jats:sec>Results<\/jats:title>When using three different immunoassays in cases with subjective cognitive decline and mild cognitive impairment, the CSF<\/jats:styled-content> A\u03b2<\/jats:italic>42\/A\u03b2<\/jats:italic>40 and A\u03b2<\/jats:italic>42\/A\u03b2<\/jats:italic>38 ratios were significantly better predictors of abnormal amyloid PET<\/jats:styled-content> than CSF<\/jats:styled-content> A\u03b2<\/jats:italic>42. Lower A\u03b2<\/jats:italic>42, A\u03b2<\/jats:italic>42\/A\u03b2<\/jats:italic>40, and A\u03b2<\/jats:italic>42\/A\u03b2<\/jats:italic>38 ratios, but not A\u03b2<\/jats:italic>40 and A\u03b2<\/jats:italic>38, correlated with smaller hippocampal volumes measured by magnetic resonance imaging. However, lower A\u03b2<\/jats:italic>38, A\u03b2<\/jats:italic>40, and A\u03b2<\/jats:italic>42, but not the ratios, correlated with non\u2010AD<\/jats:styled-content>\u2010specific subcortical changes, that is, larger lateral ventricles and white matter lesions. Further, the A\u03b2<\/jats:italic>42\/A\u03b2<\/jats:italic>40 and A\u03b2<\/jats:italic>42\/A\u03b2<\/jats:italic>38 ratios showed increased accuracy compared to A\u03b2<\/jats:italic>42 when distinguishing AD<\/jats:styled-content> from dementia with Lewy bodies or Parkinson's disease dementia and subcortical vascular dementia, where all A\u03b2<\/jats:italic>s (including A\u03b2<\/jats:italic>42) were decreased.<\/jats:p><\/jats:sec>Interpretation<\/jats:title>The CSF<\/jats:styled-content> A\u03b2<\/jats:italic>42\/A\u03b2<\/jats:italic>40 and A\u03b2<\/jats:italic>42\/A\u03b2<\/jats:italic>38 ratios are significantly better than CSF<\/jats:styled-content> A\u03b2<\/jats:italic>42 to detect brain amyloid deposition in prodromal AD<\/jats:styled-content> and to differentiate AD<\/jats:styled-content> dementia from non\u2010AD<\/jats:styled-content> dementias. The ratios reflect AD<\/jats:styled-content>\u2010type pathology better, whereas decline in CSF<\/jats:styled-content> A\u03b2<\/jats:italic>42 is also associated with non\u2010AD subcortical pathologies. These findings strongly suggest that the ratios rather than CSF<\/jats:styled-content> A\u03b2<\/jats:italic>42 should be used in the clinical work\u2010up of AD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.274","type":"journal-article","created":{"date-parts":[[2016,1,8]],"date-time":"2016-01-08T06:42:55Z","timestamp":1452235375000},"page":"154-165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":441,"title":["CSF<\/scp> A\u03b2<\/i>42\/A\u03b2<\/i>40 and A\u03b2<\/i>42\/A\u03b2<\/i>38 ratios: better diagnostic markers of Alzheimer disease"],"prefix":"10.1002","volume":"3","author":[{"given":"Shorena","family":"Janelidze","sequence":"first","affiliation":[{"name":"Clinical Memory Research Unit Department of Clinical Sciences, Malm\u00f6 Lund University Lund 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