Plaque-bearing mice with reduced levels of oligomeric amyloid-β assemblies have intact memory function

The amyloid-β (Aβ) protein exists in the aging mammalian brain in diverse assembly states, including amyloid plaques and soluble Aβ oligomers. Both forms of Aβ have been shown to impair neuronal function, but their precise roles in Alzheimer's disease (AD) -associated memory loss remain unclear. Both types of Aβ 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 Aβ assembly, Aβ*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 Aβ oligomers, on memory function. We have identified Tg2576 mice with plaques but markedly reduced levels of Aβ 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 Aβ oligomers, which occurs during a period of accelerated amyloid plaque formation. These observations support the importance of Aβ oligomers in memory loss and indicate that, at least initially, amyloid plaques do not impair memory.