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APOE genotype results in differential effects on the peripheral clearance of amyloid-beta42 in APOE knock-in and knock-out mice

Citation

Sharman, MJ and Morici, M and Hone, E and Berger, T and Taddei, K and Martins, IJ and Lim, WL and Singh, S and Wenk, M and Ghiso, J and Buxbaum, J and Gandy, S and Martins, RN, APOE genotype results in differential effects on the peripheral clearance of amyloid-beta42 in APOE knock-in and knock-out mice, Journal of Alzheimer's Disease, 2010, (21(2)) pp. 403-9. ISSN 1387-2877 (2010) [Refereed Article]

DOI: doi:10.3233/JAD-2010-100141

Abstract

The epsilon4 allele of apolipoprotein E (APOE) is currently the major genetic risk factor identified for Alzheimer's disease (AD). Previous in vivo data from our laboratory has demonstrated that amyloid-beta (Abeta) is rapidly removed from the plasma by the liver and kidney and that the rate of its clearance is affected by ApoE in C57BL/6J and APOE-/- mice. To expand upon these findings, we assessed the peripheral clearance of human synthetic Abeta42 in APOE epsilon2, epsilon3, and epsilon4 knock-in and APOE knock-out mice injected with lipidated recombinant apoE2, E3, and E4 protein. Our results show that APOE does influence the rate at which the mice are able to clear Abeta42 from their bloodstream. Both APOE epsilon4 mice and APOE knock-out mice treated with lipidated recombinant apoE4 demonstrated increased retention of plasma Abeta42 over time compared to APOE epsilon2/APOE knock-out rE2 and APOE epsilon3/APOE knock-out rE3 mice. These findings suggest that the peripheral clearance of Abeta42 is significantly altered by APOE genotype. Given that APOE epsilon4 is a risk factor for AD, then these novel findings provide some insight into the role of ApoE isoforms on the peripheral clearance of Abeta which may impact on clearance from the brain.

Item Details

Item Type:Refereed Article
Keywords:Alzheimer's disease, amyloid-, APOE genotype, peripheral sink hypothesis
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurology and Neuromuscular Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Neurodegenerative Disorders Related to Ageing
Author:Sharman, MJ (Dr Matt Sharman)
ID Code:78896
Year Published:2010
Web of Science® Times Cited:24
Deposited By:Health Sciences A
Deposited On:2012-08-02
Last Modified:2012-08-06
Downloads:0

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