Cerebrospinal Fluid A?42/40 Corresponds Better than A?42 to Amyloid PET in Alzheimer's Disease.

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