Abstract
The receptor for advanced glycation end products (RAGE) has been reported to have a pivotal role in the pathogenesis of Alzheimer's disease (AD). This study investigated RAGE levels in the hippocampus and cortex of a triple transgenic mouse model of AD (3xTg-AD) using western blotting and immunohistochemical double-labeling to assess cellular localization. Analysis of western blots showed that there were no differences in the hippocampal and cortical RAGE levels in 10-month-old adult 3xTg-AD mice, but significant increases in RAGE expression were found in the 22- to 24-month-old aged 3xTg-AD mice compared with those of age-matched controls. RAGE-positive immunoreactivity was observed primarily in neurons of aged 3xTg-AD mice with very little labeling in non-neuronal cells, with the notable exception of RAGE presence in astrocytes in the hippocampal area CA1. In addition, RAGE signals were co-localized with the intracellular amyloid precursor protein (APP)/amyloid beta (Aβ) but not with the extracellular APP/Aβ. In aged 3xTg-AD mice, expression of human tau was observed in the hippocampal area CA1 and co-localized with RAGE signals. The increased presence of RAGE in the 3xTg-AD animal model showing critical aspects of AD neuropathology indicates that RAGE may contribute to cellular dysfunction in the AD brain.
Highlights
Alzheimer’s disease (AD) is an age-related disorder characterized by cognitive impairments.[1,2] Two major pathological characteristics of AD are the formation of senile plaques (SPs) and numerous neurofibrillary tangles (NFTs)
Increased receptor for advanced glycation end products (RAGE) levels in the hippocampus and cortex of aged 3xTg-AD mice Many studies have reported that patients with AD have increased RAGE (45 kDa) levels in the brains compared with aged-matched controls.[12,13,21]
Post hoc analyses showed that the cortical RAGE levels of aged 3xTg-AD mice were significantly higher than those of the other groups (Po0.05) and differences between the other groups were not significant
Summary
Alzheimer’s disease (AD) is an age-related disorder characterized by cognitive impairments.[1,2] Two major pathological characteristics of AD are the formation of senile plaques (SPs) and numerous neurofibrillary tangles (NFTs). Deposition of amyloid beta (Ab), the main component of SPs, is found in extracellular SPs, accumulation of intraneuronal Ab is observed in patients with AD and in animal models for AD.[2,3,4,5] NFTs are composed of hyperphosphorylated tau.[6]. The receptor for advanced glycation end products (RAGE), a multiligand receptor belonging to the immunoglobulin superfamily, functions as a cell surface-binding site for advanced glycation end products (AGEs), which are adducts resulting from non-enzymatic glycation and oxidation of lipids, proteins and nucleic acids.[7] In addition, RAGE acts as a receptor for Ab, and its expression level is increased in AD brains, indicating that it has a role in the pathogenesis of neuronal dysfunction.[8] Recent studies implicate a role for RAGE in mediating the effects of AGEs on tau phosphorylation.[9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
