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RAGE does not affect amyloid pathology in transgenic ArcAbeta mice.
Neurodegener Dis. 2009; 6(5-6):270-80.ND

Abstract

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.

Authors+Show Affiliations

Division of Psychiatry Research, University of Zurich, CH-8008 Zurich, Switzerland. ivana.vodopivec @ bli.uzh.chNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20145420

Citation

Vodopivec, Ivana, et al. "RAGE Does Not Affect Amyloid Pathology in Transgenic ArcAbeta Mice." Neuro-degenerative Diseases, vol. 6, no. 5-6, 2009, pp. 270-80.
Vodopivec I, Galichet A, Knobloch M, et al. RAGE does not affect amyloid pathology in transgenic ArcAbeta mice. Neurodegener Dis. 2009;6(5-6):270-80.
Vodopivec, I., Galichet, A., Knobloch, M., Bierhaus, A., Heizmann, C. W., & Nitsch, R. M. (2009). RAGE does not affect amyloid pathology in transgenic ArcAbeta mice. Neuro-degenerative Diseases, 6(5-6), 270-80. https://doi.org/10.1159/000261723
Vodopivec I, et al. RAGE Does Not Affect Amyloid Pathology in Transgenic ArcAbeta Mice. Neurodegener Dis. 2009;6(5-6):270-80. PubMed PMID: 20145420.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - RAGE does not affect amyloid pathology in transgenic ArcAbeta mice. AU - Vodopivec,Ivana, AU - Galichet,Arnaud, AU - Knobloch,Marlen, AU - Bierhaus,Angelika, AU - Heizmann,Claus W, AU - Nitsch,Roger M, Y1 - 2010/02/10/ PY - 2009/09/09/received PY - 2009/11/18/accepted PY - 2010/2/11/entrez PY - 2010/2/11/pubmed PY - 2010/5/4/medline SP - 270 EP - 80 JF - Neuro-degenerative diseases JO - Neurodegener Dis VL - 6 IS - 5-6 N2 - 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. SN - 1660-2862 UR - https://www.unboundmedicine.com/medline/citation/20145420/RAGE_does_not_affect_amyloid_pathology_in_transgenic_ArcAbeta_mice_ L2 - https://www.karger.com?DOI=10.1159/000261723 DB - PRIME DP - Unbound Medicine ER -