期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2008
卷号：105
期号：4
页码：1343-1346
DOI：10.1073/pnas.0709906104
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Convergent evidence has revealed an association between insulin resistance and Alzheimer's disease (AD), and the peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}) agonist, rosiglitazone, an insulin sensitizer and mitochondrial activator, improves cognition in patients with early or mild-to-moderate AD. Apolipoprotein (apo) E4, a major genetic risk factor for AD, exerts neuropathological effects through multiple pathways, including impairment of dendritic spine structure and mitochondrial function. Here we show that rosiglitazone significantly increased dendritic spine density in a dose-dependent manner in cultured primary cortical rat neurons. This effect was abolished by the PPAR-{gamma}-specific antagonist, GW9662, suggesting that rosiglitazone exerts this effect by activating the PPAR-{gamma} pathway. Furthermore, the C-terminal-truncated fragment of apoE4 significantly decreased dendritic spine density. Rosiglitazone rescued this detrimental effect. Thus, rosiglitazone might improve cognition in AD patients by increasing dendritic spine density.
关键词：Alzheimer's disease ; mitochondria ; peroxisome proliferator-activated receptor-γ ; apolipoprotein E fragment ; synaptogenesis
