Complementary distributions of amyloid-beta and neprilysin in the brains of dogs and cats

Neprilysin is an amyloid-beta-degrading enzyme localized in the brain parenchyma. The involvement of neprilysin in the pathogenesis of Alzheimer's disease has recently received much attention. We examined the localization of neprilysin and amyloid-beta, as well as the activity of neprilysin, in the brains of dogs and cats of various ages to clarify the relationship between neprilysin activity and amyloid-beta deposition. The distribution of neprilysin was almost identical in dogs and cats, being high in the striatum, globus pallidus, and substantia nigra, but very low in the cerebral cortex. The white matter and hippocampus were negative. Neprilysin activity in the brain regions in dogs and cats was ranked from high to low as follows: thalamus/striatum > cerebral cortex > hippocampus > white matter. Amyloid-beta deposition was first detected at 7 and 10 years of age in dogs and cats, respectively, and both the quantity and frequency of deposition increased with age. In both species, amyloid-beta deposition appeared in the cerebral cortex and the hippocampus. In summary, the localization of neprilysin and neprilysin activity, and that of amyloid-beta, were complementary in the brains of dogs and cats.