Relationship of Cerebrospinal Fluid Markers to C-11-PiB and F-18-FDDNP Binding

The purpose of this study was to investigate the potential relationships between cerebrospinal fluid (CSF) measurements of beta-amyloid-1-42 (A beta(1-42)) and total tau to C-11-Pittsburgh compound B (C-11-PiB) and 2-(1-{6-[(2-F-18-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) malononitrile (F-18-FDDNP) binding as measured using PET. Methods: A total of 37 subjects were included, consisting of 15 patients with Alzheimer disease (AD), 12 patients with mild cognitive impairment, and 10 healthy controls. All subjects underwent a lumbar puncture and PET using both C-11-PiB and F-18-FDDNP. For both PET tracers, parametric images of binding potential were generated. Potential associations of CSF levels of A beta(1-42) and tau with C-11-PiB and F-18-FDDNP binding were assessed using Pearson correlation coefficients and linear regression analyses. Results: For both global C-11-PiB and F-18-FDDNP binding, significant correlations with CSF levels of A beta(1-42) (r = -0.72 and -0.37, respectively) and tau (r = 0.58 and 0.56, respectively) were found across groups (all P < 0.001, except P < 0.05 for correlation between F-18-FDDNP and A beta(1-42)). Linear regression analyses showed that, adjusted for regional volume, age, sex, and diagnosis, global C-11-PiB uptake had an inverse association with A beta(1-42) CSF levels (standardized beta =-0.50, P < 0.001), whereas there was a positive association between global F-18-FDDNP binding and tau CSF levels (standardized beta = 0.62, P < 0.01). Conclusion: The good agreement between these 2 different types of biomarkers (i.e., CSF and PET) provides converging evidence for their validity. The inverse association between C-11-PiB and CSF tau A beta(1-42) confirms that C-11-PiB measures amyloid load in the brain. The positive association between F-18-FDDNP and CSF tau suggests that at least part of the specific signal of F-18-FDDNP in AD patients is due to tangle formation.