title: Plaque-bearing mice with reduced levels of oligomeric amyloid-beta assemblies have intact memory function.
abstract: The amyloid-beta (Abeta) protein exists in the aging mammalian brain in diverse assembly states, including amyloid plaques and soluble Abeta oligomers. Both forms of Abeta have been shown to impair neuronal function, but their precise roles in Alzheimer's disease (AD) -associated memory loss remain unclear. Both types of Abeta are usually present at the same time in the brain, which has made it difficult to evaluate the effects of plaques and oligomers individually on memory function. Recently, a particular oligomeric Abeta assembly, Abeta 56, was found to impair memory function in the absence of amyloid plaques. Until now it has not been possible to determine the effects of plaques, in the absence of Abeta oligomers, on memory function. We have identified Tg2576 mice with plaques but markedly reduced levels of Abeta oligomers, which enabled us to study the effects of plaques alone on memory function. We found that animals with amyloid plaques have normal memory function throughout an episode of reduced Abeta oligomers, which occurs during a period of accelerated amyloid plaque formation. These observations support the importance of Abeta oligomers in memory loss and indicate that, at least initially, amyloid plaques do not impair memory.
authors.affiliation: Department of Neurology, MMC 295, 420 Delaware Street Southeast, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lesné
authors.forename: L
authors.initials: L
authors.lastname: Kotilinek
authors.forename: K H
authors.initials: KH
authors.lastname: Ashe
mesh_terms: D000367:Age Factors; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments