Exp Mol Med.  2014 Feb;46(2):e75. 10.1038/emm.2013.147.

Increased expression of the receptor for advanced glycation end products in neurons and astrocytes in a triple transgenic mouse model of Alzheimer's disease

• Choi BR
• Cho WH
• Kim J
• Lee HJ
• Chung C
• Jeon WK
• Han JS

• KMID: 2155340
• DOI: http://doi.org/10.1038/emm.2013.147

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 (Abeta) but not with the extracellular APP/Abeta. 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.

Keyword

Alzheimer's disease; astrocyte; cortex; hippocampus; mice; receptor for advanced glycation end products (RAGE)

MeSH Terms

Advanced Glycosylation End Product-Specific Receptor
Alzheimer Disease/genetics/*metabolism
Amyloid beta-Peptides/metabolism
Animals
Astrocytes/*metabolism
CA1 Region, Hippocampal/growth & development/metabolism/pathology
Humans
Mice
Mice, Transgenic
Neurons/*metabolism
Receptors, Immunologic/genetics/*metabolism
tau Proteins/genetics/metabolism
Advanced Glycosylation End Product-Specific Receptor
Amyloid beta-Peptides
Receptors, Immunologic
tau Proteins