Reduced expression of endogenous secretory receptor for advanced glycation endproducts in hippocampal neurons of Alzheimer's disease brains.
The receptor for advanced glycation endproducts (RAGE) is a cell-surface multiligand receptor, which interacts with amyloid beta (Abeta), a key protein in Alzheimer's disease (AD). RAGE-Abeta interaction is thought to be associated with pathological progression in AD. A splice variant of RAGE, endogenous secretory RAGE (esRAGE) can act as a decoy receptor for RAGE ligands that would prevent the progression of some pathologic conditions. In this study, the expression of esRAGE in the hippocampal tissues from AD brains compared with control (non-AD) was examined by immunohistochemistry and Western blot analysis. Semiquantitative immunohistochemical analysis of hippocampal tissues using esRAGE-specific antibody revealed significantly decreased immunoreactivities in pyramidal cells in CA1 and CA3 regions of AD compared with non-AD. On the other hand, immunoreactivities of astrocytes for esRAGE significantly increased in those regions. Dentate granule cells and astrocytes showed essentially invariant immunoreactivities between AD and non-AD. Changes in esRAGE immunoreactivity in CA3 neurons and astrocytes were observed from the early pathological stages. Moreover, the esRAGE-immunoreactive bands of AD samples were weaker than those of non-AD samples in Western blot analysis. The results indicate that low expression of esRAGE in the hippocampus would be associated with the development of AD.
Nozaki
Ichiro
I
Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Watanabe
Takuo
T
Kawaguchi
Makoto
M
Akatsu
Hiroyasu
H
Tsuneyama
Koichi
K
Yamamoto
Yasuhiko
Y
Ohe
Kazuyo
K
Yonekura
Hideto
H
Yamada
Masahito
M
Yamamoto
Hiroshi
H
D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic