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ABSTRACT: Background
Decreased concentrations of amyloid-? 1-42 (A?42) in cerebrospinal fluid (CSF) and increased retention of A? tracers in the brain on positron emission tomography (PET) are considered the earliest biomarkers of Alzheimer's disease (AD). However, a proportion of cases show discrepancies between the results of the two biomarker modalities which may reflect inter-individual differences in A? metabolism. The CSF A?42/40 ratio seems to be a more accurate biomarker of clinical AD than CSF A?42 alone.Objective
We tested whether CSF A?42 alone or the A?42/40 ratio corresponds better with amyloid PET status and analyzed the distribution of cases with discordant CSF-PET results.Methods
CSF obtained from a mixed cohort (n?=?200) of cognitively normal and abnormal research participants who had undergone amyloid PET within 12 months (n?=?150 PET-negative, n?=?50 PET-positive according to a previously published cut-off) was assayed for A?42 and A?40 using two recently developed immunoassays. Optimal CSF cut-offs for amyloid positivity were calculated, and concordance was tested by comparison of the areas under receiver operating characteristic (ROC) curves (AUC) and McNemar's test for paired proportions.Results
CSF A?42/40 corresponded better than A?42 with PET results, with a larger proportion of concordant cases (89.4% versus 74.9%, respectively, p?ConclusionThe CSF A?42/40 ratio is superior to A?42 alone as a marker of amyloid-positivity by PET. We hypothesize that this increase in performance reflects the ratio compensating for general between-individual variations in CSF total A?.
SUBMITTER: Lewczuk P
PROVIDER: S-EPMC5147502 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
Lewczuk Piotr P Matzen Anja A Blennow Kaj K Parnetti Lucilla L Molinuevo Jose Luis JL Eusebi Paolo P Kornhuber Johannes J Morris John C JC Fagan Anne M AM
Journal of Alzheimer's disease : JAD 20170101 2
<h4>Background</h4>Decreased concentrations of amyloid-β 1-42 (Aβ42) in cerebrospinal fluid (CSF) and increased retention of Aβ tracers in the brain on positron emission tomography (PET) are considered the earliest biomarkers of Alzheimer's disease (AD). However, a proportion of cases show discrepancies between the results of the two biomarker modalities which may reflect inter-individual differences in Aβ metabolism. The CSF Aβ42/40 ratio seems to be a more accurate biomarker of clinical AD tha ...[more]