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Gene delivery of human apolipoprotein E alters brain Abeta burden in a mouse model of Alzheimer's disease.
Proc Natl Acad Sci U S A 2005; 102(4):1211-6PN

Abstract

Apolipoprotein E (apoE) alleles are important genetic risk factors for Alzheimer's disease (AD), with the epsilon4 allele increasing and the epsilon2 allele decreasing risk for developing AD. ApoE has been shown to influence brain amyloid-beta peptide (Abeta) and amyloid burden, both in humans and in transgenic mice. Here we show that direct intracerebral administration of lentiviral vectors expressing the three common human apoE isoforms differentially alters hippocampal Abeta and amyloid burden in the PDAPP mouse model of AD. Expression of apoE4 in the absence of mouse apoE increases hippocampal Abeta(1-42) levels and amyloid burden. By contrast, expression of apoE2, even in the presence of mouse apoE, markedly reduces hippocampal Abeta burden. Our data demonstrate rapid apoE isoform-dependent effects on brain Abeta burden in a mouse model of AD. Gene delivery of apoE2 may prevent or reduce brain Abeta burden and the subsequent development of neuritic plaques.

Authors+Show Affiliations

Neuroscience Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.No affiliation info availableNo 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

15657137

Citation

Dodart, Jean-Cosme, et al. "Gene Delivery of Human Apolipoprotein E Alters Brain Abeta Burden in a Mouse Model of Alzheimer's Disease." Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 4, 2005, pp. 1211-6.
Dodart JC, Marr RA, Koistinaho M, et al. Gene delivery of human apolipoprotein E alters brain Abeta burden in a mouse model of Alzheimer's disease. Proc Natl Acad Sci USA. 2005;102(4):1211-6.
Dodart, J. C., Marr, R. A., Koistinaho, M., Gregersen, B. M., Malkani, S., Verma, I. M., & Paul, S. M. (2005). Gene delivery of human apolipoprotein E alters brain Abeta burden in a mouse model of Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America, 102(4), pp. 1211-6.
Dodart JC, et al. Gene Delivery of Human Apolipoprotein E Alters Brain Abeta Burden in a Mouse Model of Alzheimer's Disease. Proc Natl Acad Sci USA. 2005 Jan 25;102(4):1211-6. PubMed PMID: 15657137.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gene delivery of human apolipoprotein E alters brain Abeta burden in a mouse model of Alzheimer's disease. AU - Dodart,Jean-Cosme, AU - Marr,Robert A, AU - Koistinaho,Milla, AU - Gregersen,Beth M, AU - Malkani,Seema, AU - Verma,Inder M, AU - Paul,Steven M, Y1 - 2005/01/18/ PY - 2005/1/20/pubmed PY - 2005/3/2/medline PY - 2005/1/20/entrez SP - 1211 EP - 6 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 102 IS - 4 N2 - Apolipoprotein E (apoE) alleles are important genetic risk factors for Alzheimer's disease (AD), with the epsilon4 allele increasing and the epsilon2 allele decreasing risk for developing AD. ApoE has been shown to influence brain amyloid-beta peptide (Abeta) and amyloid burden, both in humans and in transgenic mice. Here we show that direct intracerebral administration of lentiviral vectors expressing the three common human apoE isoforms differentially alters hippocampal Abeta and amyloid burden in the PDAPP mouse model of AD. Expression of apoE4 in the absence of mouse apoE increases hippocampal Abeta(1-42) levels and amyloid burden. By contrast, expression of apoE2, even in the presence of mouse apoE, markedly reduces hippocampal Abeta burden. Our data demonstrate rapid apoE isoform-dependent effects on brain Abeta burden in a mouse model of AD. Gene delivery of apoE2 may prevent or reduce brain Abeta burden and the subsequent development of neuritic plaques. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/15657137/Gene_delivery_of_human_apolipoprotein_E_alters_brain_Abeta_burden_in_a_mouse_model_of_Alzheimer's_disease_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=15657137 DB - PRIME DP - Unbound Medicine ER -