APOE Genotype Results in Differential Effects on the Peripheral Clearance of Amyloid-ß42 in APOE Knock-in and Knock-out Mice

Document Type

Journal Article

Publisher

IOS Press

Faculty

Faculty of Computing, Health and Science

School

School of Exercise, Biomedical and Health Science / Centre of Excellence for Alzheimer's Disease Research and Care

RAS ID

10480

Comments

Sharman, M. J., Morici, M., Hone, E., Berger, T., Taddei, K. , Martins, I. J., Lim, W., Singh, S. , Wenk, M., Ghiso, J., Buxbaum, J., Gandy, S. , & Martins, R. N. (2010). APOE Genotype Results in Differential Effects on the Peripheral Clearance of Amyloid-ß42 in APOE Knock-in and Knock-out Mice. Journal of Alzheimer's Disease, 21(2), 403-409. Available here

Abstract

The ε4 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-β (Aβ) 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 Aβ42 in APOE ε2, ε3, and ε4 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 Aβ42 from their bloodstream. Both APOE ε4 mice and APOE knock-out mice treated with lipidated recombinant apoE4 demonstrated increased retention of plasma Aβ42 over time compared to APOE ε2/APOE knock-out rE2 and APOE ε3/APOE knock-out rE3 mice. These findings suggest that the peripheral clearance of Aβ42 is significantly altered by APOE genotype. Given that APOE ε4 is a risk factor for AD, then these novel findings provide some insight into the role of ApoE isoforms on the peripheral clearance of Aβ which may impact on clearance from the brain.

DOI

10.3233/JAD-2010-100141

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Link to publisher version (DOI)

10.3233/JAD-2010-100141