有关AD转基因小鼠的文献1.pdfVIP

Vol 440 |16 March 2006|doi:10.1038/nature04533 LETTERS A specific amyloid-b protein assembly in the brain impairs memory ´1 4 1 6 6 7 Sylvain Lesne , Ming Teng Koh , Linda Kotilinek , Rakez Kayed , Charles G. Glabe , Austin Yang , Michela Gallagher4 Karen H. Ashe1,2,3,5 1 Memory function often declines with age , and is believed to for memory loss, is associated with no change in memory function. deteriorate initially because of changes in synaptic function rather One solution to this conundrum is to posit the existence of soluble than loss of neurons2. Some individuals then go on to develop Ab assemblies that disrupt memory6,14–16, which we designated Ab * b star) and sought to identify in Tg2576 mice. Alzheimer’s disease with neurodegeneration. Here we use Tg2576 (A b precursor protein (APP) A challenge in analysing Ab in the brain lies in reliably separating mice, which express a human amyloid- variant linked to Alzheimer’s disease, to investigate the cause of the specific cellular pools of Ab (for example, extracellular, intra- b cellular, membrane-associated and insoluble). We overcame this memory decline in the absence of neurodegeneration or amyloid- protein amyloidosis. Young Tg2576 mice (6 months old) have obstacle by developing a high-fidelity extraction procedure that normal memory and lack