Comparing Positron Emission Tomography Imaging and Cerebrospinal Fluid Measurements of β-Amyloid

ObjectiveWe examined agreement and disagreement between 2 biomarkers of beta-amyloid (A) deposition (amyloid positron emission tomography [PET] and cerebrospinal fluid [CSF] A(1-42)) in normal aging and dementia in a large multicenter study. MethodsConcurrently acquired florbetapir PET and CSF A were measured in cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease participants (n=374) from the Alzheimer's Disease Neuroimaging Initiative. We also compared A measurements in a separate group with serial CSF measurements over 3.10.8 years that preceded a single florbetapir session. Additional biomarker and cognitive data allowed us to further examine profiles of discordant cases. ResultsFlorbetapir and CSF A were inversely correlated across all diagnostic groups, and dichotomous measurements were in agreement in 86% of subjects. Among subjects showing the most disagreement, the 2 discordant groups had different profiles: the florbetapir(+)/CSF A(-) group was larger (n=13) and was made up of only normal and early MCI subjects, whereas the florbetapir(-)/CSF A(+) group was smaller (n=7) and had poorer cognitive function and higher CSF tau, but no ApoE4 carriers. In the longitudinal sample, we observed both stable longitudinal CSF A trajectories and those actively transitioning from normal to abnormal, but the final CSF A measurements were in good agreement with florbetapir cortical retention. InterpretationCSF and amyloid PET measurements of A were consistent in the majority of subjects in the cross-sectional and longitudinal populations. Based on our analysis of discordant subjects, the available evidence did not show that CSF A regularly becomes abnormal prior to fibrillar A accumulation early in the course of disease. Ann Neurol 2013;74:826-836