Insulin increases CSF Aβ42 levels in normal older adults
Insulin increases CSF Aβ42 levels in normal older adults
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DOI：
10.1212/01.wnl.0000065916.25128.25
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发表时间：
2003-06-24
期刊：
影响因子：
9.9
通讯作者：
Craft, S
中科院分区：
文献类型：
--
作者：
Watson, GS;Peskind, ER;Craft, S
背景：胰岛素代谢异常可能参与AD的临床症状和病理生理过程。体外研究表明，胰岛素可增强β-淀粉样蛋白（Abeta）的释放或抑制其降解，这两种作用均可能增加淀粉样蛋白负荷。研究方法：在不同的早晨，16名健康老年人（10名女性，6名男性;平均年龄68.7岁，SD 8.6岁）每人接受两次输注，包括生理盐水（安慰剂）或胰岛素（1.0 mU）。kg（-1）.min（-1））加葡萄糖维持正常。输注120分钟后，采集血液、CSF和认知测量值。结果：正如预期，胰岛素输注引起CSF胰岛素浓度增加。胰岛素输注还导致CSF A β 42水平升高，尤其是在老年受试者中。如先前所观察到的，胰岛素输注促进陈述性记忆，但这种促进作用在CSF A β 42水平增加最大的受试者中减弱。结论：这些发现与胰岛素对Abeta影响的最新体外研究一致，并支持胰岛素可急性调节人体Abeta 42水平的观点。
Background: Abnormal insulin metabolism may contribute to the clinical symptoms and pathophysiology of AD. In vitro studies show that insulin enhances the release of beta- amyloid protein ( Abeta) or inhibits its degradation, either of which might increase amyloid burden. Methods: On separate mornings, 16 healthy older adults ( 10 women, 6 men; mean age 68.7 years, SD 8.6 years) each underwent two infusions consisting of either saline ( placebo) or insulin ( 1.0 mU. kg(-1).min(-1)) plus dextrose to maintain euglycemia. After 120 minutes of infusion, blood, CSF, and cognitive measures were acquired. Results: As expected, insulin infusion produced an increase in CSF insulin concentration. Insulin infusion also led to an increase in CSF Abeta42 levels, most notably in older subjects. As has been observed previously, insulin infusion facilitated declarative memory, but such facilitation was attenuated in the subjects with the greatest increase in CSF Abeta42 levels. Conclusions: These findings are consistent with recent in vitro studies of insulin effects on Abeta and support the notion that insulin may modulate Abeta42 levels acutely in humans.