Analysis of Expression of the Amyloid-Degrading Enzyme Neprilysin in Brain Structures of 5xFAD Transgenic Mice

Neprilysin (NEP) is a neuropeptidase participating in transmission of various neuronal stimuli. It is also a major amyloid (A beta)-degrading enzyme in the brain and its deficit can lead to neurodegeneration and development of Alzheimer's disease (AD). As we have recently shown in rats, NEP is highly expressed in the olfactory bulbs, and its decreased levels in these brain structures, involved in olfaction, correlate with impaired sense of smell. In this study we analysed NEP expression in the brain structures of adult 5xFAD mice modelling AD which progressively accumulate A beta with age, compared to the wild type C57Bl mice. We have found that in the C57Bl mice, like in rats, the highest NEP mRNA levels are in the striatum (Str) and olfactory bulbs (OB) whereas in the entorhinal cortex (EC), parietal cortex (PC) and hippocampus (Hip) they are about 5 times lower than in the Str. In 5xFAD mice, levels of NEP mRNA in the Str and OB were not different from the wild type animals whereas in the EC, PC and Hip they were decreased by approx. 30% compared to the wild type mice. This decrease in NEP expression in the EC, PC and Hip of the 5xFAD mice correlated with accumulation of A beta, impaired cognition (the Morris water maze test) and olfaction (the odour preference test) compared to the wild type mice. Our data support the suggestion that impaired olfactory function characteristic of AD might be related to decreased expression of NEP in the brain structures processing olfactory stimuli, in particular the EC and Hip.