Altered Brain Adiponectin Receptor Expression in the 5XFAD Mouse Model of Alzheimer's Disease.

Anishchal A Pratap,R M Damian Holsinger

doi:10.3390/ph13070150

Abstract

Metabolic syndromes share common pathologies with Alzheimer’s disease (AD). Adiponectin, an adipocyte-derived protein, regulates energy metabolism via its receptors, AdipoR1 and AdipoR2. To investigate the distribution of adiponectin receptors (AdipoRs) in Alzheimer’s, we examined their expression in the aged 5XFAD mouse model of AD. In age-matched wild-type mice, we observed neuronal expression of both ARs throughout the brain as well as endothelial expression of AdipoR1. The pattern of receptor expression in the aged 5XFAD brain was significantly perturbed. Here, we observed decreased neuronal expression of both ARs and decreased endothelial expression of AdipoR1, but robust expression of AdipoR2 in activated astrocytes. We also observed AdipoR2-expressing astrocytes in the dorsomedial hypothalamic and thalamic mediodorsal nuclei, suggesting the possibility that astrocytes utilise AdipoR2 signalling to fuel their activated state in the AD brain. These findings provide further evidence of a metabolic disturbance and demonstrate a potential shift in energy utilisation in the AD brain, supporting imaging studies performed in AD patients.

Highlights

Alzheimer’s disease (AD) is a neurodegenerative disorder that represents approximately 60–80% of all cases of dementia [1]
AdipoR1 and AdipoR2 Is Expressed throughout the Mouse Cortex and Hippocampus
Similar to previous reports [48], we found that AdipoR1 and AdipoR2 is expressed in neurons throughout the cortex of 48–52-week-old, aged wild-type (WT) and 5XFAD mice

Summary

Introduction

Alzheimer’s disease (AD) is a neurodegenerative disorder that represents approximately 60–80% of all cases of dementia [1]. Aging is by far the most prevalent risk factor for the development of AD, with 95% of patients being diagnosed over the age of 65 [2]. These cases have no clear aetiology, nor mechanisms of onset. Alzheimer’s is a multifactorial disease with various genetic, environmental, and epigenetic factors that can lead to excessive accumulation of Aβ in the brain. Unhealthy diets and a lack of exercise can cause metabolic syndromes, such as obesity, type 2 diabetes mellitus, hypercholesterolemia, hypertension, and atherosclerosis, which may create a knock-on effect leading to AD-associated pathologies later in life [18,19,20,21,22]

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