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PMID: 15657137 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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 ·2005-01-25 ·Pages 1211-6

Dodart JC, Marr RA, Koistinaho M, Gregersen BM, Malkani S, Verma IM, Paul SM

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.

MeSH Terms
Alzheimer Disease/metabolism,therapy Amyloid beta-Peptides/metabolism Animals Apolipoprotein E2 Apolipoproteins E/genetics Brain/metabolism Disease Models, Animal Genetic Therapy Hippocampus/metabolism Humans Lentivirus/genetics Mice Mice, Transgenic
Chemicals
Amyloid beta-Peptides Apolipoprotein E2 Apolipoproteins E
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Dodart Jean-Cosme
Neuroscience Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Marr Robert A
Koistinaho Milla
Gregersen Beth M
Malkani Seema
Verma Inder M
Paul Steven M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0409072102
Published
2005-01-25
Epub
2005-00-18
Pages
1211-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC544620
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0409072102 PMC Full Text View journal details
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