Neprilysin Is Poorly Expressed in the Prefrontal Cortex of Aged Dogs with Cognitive Dysfunction Syndrome

Jesús Canudas,María Luisa Suárez,Leticia Sarasa,Daniel Insua,Pedro Pesini,Ángela González-Martínez,Manuel Sarasa,Germán Santamarina

doi:10.1155/2014/483281

Abstract

Neprilysin (NEP) is the principal amyloid β (Aβ) degrading peptidase; this activity may protect against Alzheimer's disease (AD), the most important age-related neurodegenerative process. The aim of this work was to analyze NEP mRNA expression in the frontal cortex of dogs with and without canine cognitive dysfunction syndrome (CDS), which is considered a natural model for AD. Expression of canine cerebral NEP mRNA was assessed by RT-PCR followed by qPCR in young, aged-cognitively unimpaired (CU), and aged-cognitively impaired (CI) dogs. On average, aged-CI dogs showed 80% (P < 0.01) lower expression levels of NEP mRNA than their aged-CU counterparts. Furthermore, the standard deviation of the qPCR measurements was more than 6 times higher in the cognitively healthy animals (young and aged-CU) than in the aged-CI group. Another interesting find is the determination of a positive correlation between NEP expression and the number of cholinergic neurons in basal telencephalon, indicating a probable connection between both events in these types of neurodegeneration processes. These results suggest that high expression levels of NEP might be a protective factor for canine CDS and, most likely, for other Aβ-associated neurodegenerative diseases, such as AD.

Highlights

Amyloid β (Aβ) peptides are considered to be the main agents implicated in Alzheimer’s disease (AD), the most common dementia [1]
We have investigated the expression of NEP mRNA in the prefrontal cortex of the dog, an early affected region in cognitive dysfunction syndrome (CDS) and AD, to explore if there are differences in cortical NEP expression related to age or cognitive status
Whereas insulin-degrading enzyme (IDE) mRNA was homogenously expressed in all the animals at similar levels than Ubi, NEP mRNA expression varied in both intragroup and intergroups of animals

Summary

Introduction

Amyloid β (Aβ) peptides are considered to be the main agents implicated in Alzheimer’s disease (AD), the most common dementia [1]. In other studies, NEP protein levels did not correlate with age in human controls, NEP activity being significantly higher in elderly than in younger people [12]. Another significant investigation has shown that mice overexpressing both NEP and human APP, with the Swedish and Indiana mutations, in neurons had reduced brain Aβ burdens and presented less cognitive impairment [13]. All these findings suggest that NEP may play an important protective role against AD and could be an important therapeutic target [14]

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