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Updated: Jun 16, 2026
Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus
Published on: June 17, 2015
RAGE does not affect amyloid pathology in transgenic ArcAbeta mice
Ivana Vodopivec1, Arnaud Galichet, Marlen Knobloch
1Division of Psychiatry Research, University of Zurich, CH-8008 Zurich, Switzerland. ivana.vodopivec @ bli.uzh.ch
Background:
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.
Objective:
Our purpose was to assess the effect of RAGE deletion on Abeta-related pathology.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Deleting the receptor for advanced glycation end products (RAGE) in a mouse model of Alzheimer's disease (AD) increased insulin-degrading enzyme activity but did not prevent cognitive decline or amyloid-beta (Abeta) accumulation.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Alzheimer's disease (AD) involves brain accumulation of amyloid-beta (Abeta) peptides, triggering pathological processes.
- The receptor for advanced glycation end products (RAGE) binds Abeta and is implicated in AD pathogenesis.
Purpose of the Study:
- To investigate the impact of RAGE deletion on Abeta-related pathology in a mouse model of AD.
Main Methods:
- Crossed RAGE knockout mice with arcAbeta mice (transgenic for Swedish and Arctic Abeta precursor protein mutations).
- Assessed Abeta levels, brain deposition, enzyme activities, protein expression, microglia characteristics, and cognitive performance at 6 and 12 months.
Main Results:
- RAGE deletion reduced cortical and hippocampal Abeta levels and increased insulin-degrading enzyme activity at 6 months.
- Cognitive decline and age-related Abeta accumulation were not prevented by RAGE deletion.
- No differences in microglia area or morphology were observed between RAGE(-/-)/arcAbeta and arcAbeta mice.
Conclusions:
- Absence of RAGE increased insulin-degrading enzyme activity but did not ameliorate cognitive deficits, Abeta accumulation, or microglial activation in this AD mouse model.
