Hippocampal infusions of apolipoprotein E peptides induce long-lasting cognitive impairment.

Journal Article (Journal Article)

The inheritance of the varepsilon4 allele of apolipoprotein E (ApoE4) and cholinergic system dysfunction have long been associated with the pathology of Alzheimer's disease (AD). Recently, in vitro studies have established a direct link between ApoE and cholinergic function in that synthetic peptides containing segments of the ApoE protein (ApoE(133-149) and ApoE(141-148)) interact with alpha7 nicotinic acetylcholine receptors (nAChRs) in the hippocampus. This raises the possibility that ApoE peptides may contribute to cognitive impairment in AD in that the hippocampus plays a key role in cognitive functioning. To test this, we acutely infused ApoE peptides into the ventral hippocampus of female Sprague-Dawley rats and assessed the resultant effects on radial-arm maze choice accuracy over a period of weeks after the infusion. Local ventral hippocampal infusion of ApoE peptides caused significant cognitive impairment in radial-arm maze learning that persisted several weeks after the acute infusion. This persisting deficit may be an important model for understanding the relationship between ApoE protein-induced neurotoxicity and cognitive impairment as well as serve as a platform for the development of new therapies to avoid neurotoxicity and cognitive decline.

Full Text

Duke Authors

Cited Authors

  • Eddins, D; Klein, RC; Yakel, JL; Levin, ED

Published Date

  • April 29, 2009

Published In

Volume / Issue

  • 79 / 2

Start / End Page

  • 111 - 115

PubMed ID

  • 19185602

Pubmed Central ID

  • PMC4770792

Electronic International Standard Serial Number (EISSN)

  • 1873-2747

Digital Object Identifier (DOI)

  • 10.1016/j.brainresbull.2009.01.003


  • eng

Conference Location

  • United States