RAGE does not affect amyloid pathology in transgenic ArcAbeta mice.

Détails

ID Serval
serval:BIB_9B0636FF6D2F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
RAGE does not affect amyloid pathology in transgenic ArcAbeta mice.
Périodique
Neuro-degenerative diseases
Auteur(s)
Vodopivec I., Galichet A., Knobloch M., Bierhaus A., Heizmann C.W., Nitsch R.M.
ISSN
1660-2862 (Electronic)
ISSN-L
1660-2854
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
6
Numéro
5-6
Pages
270-280
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Alzheimer's disease (AD) is characterized by brain accumulation of the amyloid-beta peptide (Abeta) that triggers a cascade of biochemical and cellular alterations resulting in the clinical phenotype of the disease. While numerous experiments addressed Abeta toxicity, the mechanisms are still not fully understood. The receptor for advanced glycation end products (RAGE) binds Abeta and was suggested to be involved in the pathological processes of AD.
Our purpose was to assess the effect of RAGE deletion on Abeta-related pathology.
We crossed RAGE knockout (RAGE(-/-)) mice with transgenic mice harboring both the Swedish and Arctic Abeta precursor protein mutations (arcAbeta mice). We assessed Abeta levels, Abeta brain deposition, Abeta-degrading enzyme activities, Abeta precursor protein expression and processing, number and morphology of microglia as well as cognitive performance of 6- and 12-month-old RAGE(-/-)/arcAbeta, RAGE(-/-), arcAbeta and wild-type mice.
RAGE(-/-)/arcAbeta mice had significantly lower levels of SDS- and formic-acid-extracted Abeta in the cortex and hippocampus, with concomitantly increased activity of insulin-degrading enzyme at the age of 6 months. However, RAGE deletion could neither prevent the decline in cognitive performance nor the age-related cerebral accumulation of Abeta peptide. Furthermore, histological analysis revealed no difference in the microglia-occupied brain areas or microglial morphologies between RAGE(-/-)/arcAbeta and arcAbeta mice.
Together, our results indicate that while the absence of RAGE was associated with increased insulin-degrading enzyme activity in the brain, it was not sufficient to prevent or ameliorate cognitive deterioration, Abeta accumulation and microglial activation in the arcAbeta mouse model of AD.
Mots-clé
Age Factors, Alzheimer Disease/genetics, Alzheimer Disease/metabolism, Alzheimer Disease/pathology, Alzheimer Disease/physiopathology, Amyloid beta-Peptides/genetics, Amyloid beta-Peptides/metabolism, Amyloid beta-Protein Precursor/genetics, Amyloid beta-Protein Precursor/metabolism, Animals, Brain/metabolism, Brain/pathology, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay/methods, Gene Expression Regulation/genetics, Humans, Maze Learning/physiology, Mice, Mice, Transgenic, Peptide Fragments/metabolism, Receptor for Advanced Glycation End Products, Receptors, Immunologic/genetics, Receptors, Immunologic/metabolism, Statistics as Topic
Pubmed
Web of science
Création de la notice
25/05/2018 9:41
Dernière modification de la notice
20/08/2019 16:02
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