CSF biomarkers and amyloid PET: concordance and diagnostic accuracy in a MCI cohort.

Abstract

Brain amyloid deposition is one of the main hallmarks of Alzheimer's disease (AD) and two approaches are available for assessing amyloid pathology in vivo: cerebrospinal fluid (CSF) biomarkers levels and amyloid load visualized by amyloid beta positron emission tomography imaging (Amy-PET) probes. We aimed to investigate the concordance between CSF biomarkers and Amy-PET in a memory clinic cohort. Moreover, using a proper clinical follow-up, we wanted to assess the diagnostic accuracy of CSF and PET biomarkers in predicting the progression of patients with mild cognitive impairment (MCI) to AD dementia. We included 31 MCI patients who underwent [18F]florbetaben PET and CSF sampling (Aβ1-42, t-Tau, p-Tau). A semiquantitative visual scan assessment was used to quantify amyloid deposition in 5 brain regions, rating from 1 (negative), to 2 and 3 (positive). CSF biomarkers were considered abnormal if: Aβ1-42 < 600pg/ml, p-Tau/Aβ1-42 > 0.08 and t-Tau/Aβ1-42 > 0.52. We also applied less lenient cutoffs of 550pg/ml and 450pg/ml for Aβ1-42. The concordance rate was 77% between Amy-PET and CSF Aβ1-42 levels, and 89% between Amy-PET and p-Tau/Aβ1-42 and t-Tau/Aβ1-42. According to the clinical follow-up, Amy-PET (sensitivity [SE] 93.7%, specificity [SP] 80%) exhibited the best diagnostic accuracy in discriminating AD from non-AD, followed by p-Tau/Aβ1-42 ratio and t-Tau/Aβ1-42 ratio (SE 93.7%, SP 66.6%), and Aβ1-42 levels (SE 81%, SP 60%). The regional uptake of [18F]florbetaben PET in the precuneus and the striatum showed the best SP (86.6%). In discordant cases, the clinical diagnosis was most often in agreement with PET results. In general, concordance between CSF biomarkers and Amy-PET was good, especially when the ratios between CSF amyloid and Tau biomarkers were used. However, Amy-PET proved to be superior to CSF Aβ1-42 in terms of diagnostic accuracy for AD, with the possibility to further increase its specificity by focusing the analysis in specific areas such as the precuneus/posterior cingulate cortex and the striatum.