Relationship of Cerebrospinal Fluid Markers to11C-PiB and18F-FDDNP Binding

Abstract

The purpose of this study was to investigate the potential relationships between cerebrospinal fluid (CSF) measurements of β-amyloid-1–42 (Aβ_1-42) and total tau to ¹¹C-Pittsburgh compound B (¹¹C-PiB) and 2-(1-{6-[(2-¹⁸F-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) malononitrile (¹⁸F-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 ¹¹C-PiB and ¹⁸F-FDDNP. For both PET tracers, parametric images of binding potential were generated. Potential associations of CSF levels of Aβ_1-42 and tau with ¹¹C-PiB and ¹⁸F-FDDNP binding were assessed using Pearson correlation coefficients and linear regression analyses. Results: For both global ¹¹C-PiB and ¹⁸F-FDDNP binding, significant correlations with CSF levels of Aβ_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 ¹⁸F-FDDNP and Aβ_1-42). Linear regression analyses showed that, adjusted for regional volume, age, sex, and diagnosis, global ¹¹C-PiB uptake had an inverse association with Aβ_1-42 CSF levels (standardized β = −0.50, P < 0.001), whereas there was a positive association between global ¹⁸F-FDDNP binding and tau CSF levels (standardized β = 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 ¹¹C-PiB and CSF tau Aβ_1-42 confirms that ¹¹C-PiB measures amyloid load in the brain. The positive association between ¹⁸F-FDDNP and CSF tau suggests that at least part of the specific signal of ¹⁸F-FDDNP in AD patients is due to tangle formation.