Abstract
Background: Neprilysin (NEP) cleaves amyloid-β 1–42 (Aβ<sub>42</sub>) in the brain. Hence, we aimed to elucidate the effect of NEP on Aβ<sub>42</sub> in cerebrospinal fluid (CSF) and on in vivo brain amyloid load using amyloid positron emission tomography (PET) with [<sup>11</sup>C]PiB (Pittsburgh compound B). In addition, associations with the biomarkers for neuronal injury, CSF-tau and FDG-PET, were investigated. Methods: Associations were calculated using global and voxel-based (SPM8) linear regression analyses in the same cohort of 23 highly characterized Alzheimer’s disease patients. Results: CSF-NEP was significantly inversely associated with CSF-Aβ<sub>42</sub> and positively with the extent of neuronal injury as measured by CSF-tau and FDG-PET. Conclusions: Our results on CSF-NEP are compatible with the assumption that local degradation, amongst other mechanisms of amyloid clearance, plays a role in the development of Alzheimer’s pathology. In addition, CSF-NEP is associated with the extent and the rate of neurodegeneration.
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