Cerebrospinal fluid BACE1 activity and brain amyloid load in Alzheimer's disease.

The secretase BACE1 is fundamentally involved in the development of cerebral amyloid pathology in Alzheimer's disease (AD). It has not been studied so far to what extent BACE1 activity in cerebrospinal fluid (CSF) mirrors in vivo amyloid load in AD. We explored associations between CSF BACE1 activity and fibrillar amyloid pathology as measured by carbon-11-labelled Pittsburgh Compound B positron emission tomography ([¹¹C]PIB PET). [¹¹C]PIB and CSF studies were performed in 31 patients with AD. Voxel-based linear regression analysis revealed significant associations between CSF BACE1 activity and [¹¹C]PIB tracer uptake in the bilateral parahippocampal region, the thalamus, and the pons. Our study provides evidence for a brain region-specific correlation between CSF BACE1 activity and in-vivo fibrillar amyloid pathology in AD. Associations were found in areas close to the brain ventricles, which may have important implications for the use of BACE1 in CSF as a marker for AD pathology and for antiamyloid treatment monitoring.

Quantification of [18F]diprenorphine kinetics in the human brain with compartmental and non-compartmental modeling approaches.

6-O-(2-[(18)F]fluoroethyl)-6-O-desmethyldiprenorphine ([(18)F]FDPN) is a nonselective opiate ligand that binds to postsynaptic micro, kappa and delta opiate receptors. Due to the longer half-life of F-18, compared to C-11, labeling DPN with F-18 allows for alternative experimental protocols and potentially the evaluation of endogenous opioid release. The applicability of this compound to assorted experimental protocols motivated the evaluation of [(18)F]FDPN kinetics with compartmental and non-compartmental models. The results indicate that a two-tissue compartmental model best characterizes the data obtained following a bolus injection of [(18)F]FDPN (120-min scanning protocol). Estimates of distribution volume (DV) were robust, being highly correlated for the one-tissue compartmental model as well as the invasive Logan model and the basis function method. Furthermore, the DV estimates were also stable under a shortened protocol of 60 min, showing a significant correlation with the full protocol. The binding potential (BP) values showed more variability between methods and in some cases were more sensitive to protocol length. In conclusion, this evaluation of [(18)F]FDPN kinetics illustrates that DV values can be estimated robustly using compartmental modeling, the basis function method or the invasive Logan modeling approach on a volume of interest level. BP values were also found to correlate with DV values; however, these results should be interpreted with the understanding that specific binding in the reference region (occipital region) may exist.