Lesné S, Kotilinek L, Ashe K H
Department of Neurology, MMC 295, 420 Delaware Street Southeast, University of Minnesota, Minneapolis, MN 55455, USA.
Neuroscience. 2008 Feb 6;151(3):745-9. doi: 10.1016/j.neuroscience.2007.10.054. Epub 2007 Nov 17.
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.
β-淀粉样蛋白（Aβ）以多种组装状态存在于衰老的哺乳动物大脑中，包括淀粉样斑块和可溶性Aβ寡聚体。两种形式的Aβ均已被证明会损害神经元功能，但其在阿尔茨海默病（AD）相关记忆丧失中的精确作用仍不清楚。两种类型的Aβ通常同时存在于大脑中，这使得难以单独评估斑块和寡聚体对记忆功能的影响。最近，发现一种特殊的寡聚Aβ组装体Aβ56在没有淀粉样斑块的情况下会损害记忆功能。到目前为止，尚无法确定在没有Aβ寡聚体的情况下斑块对记忆功能的影响。我们鉴定出了有斑块但Aβ寡聚体水平显著降低的Tg2576小鼠，这使我们能够单独研究斑块对记忆功能的影响。我们发现，在Aβ寡聚体减少的整个过程中，有淀粉样斑块的动物具有正常的记忆功能，Aβ寡聚体减少发生在淀粉样斑块形成加速的时期。这些观察结果支持了Aβ寡聚体在记忆丧失中的重要性，并表明至少在最初，淀粉样斑块不会损害记忆。
