Caffeine suppresses amyloid-beta levels in plasma and brain of Alzheimer's disease transgenic mice.
Caffeine suppresses amyloid-beta levels in plasma and brain of Alzheimer's disease transgenic mice.
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DOI：
10.3233/jad-2009-1071
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Potter H
中科院分区：
文献类型：
--
作者：
Cao C;Cirrito JR;Lin X;Wang L;Verges DK;Dickson A;Mamcarz M;Zhang C;Mori T;Arendash GW;Holtzman DM;Potter H
最近的流行病学研究表明，咖啡因可能对阿尔茨海默病（AD）有保护作用。支持这一前提，我们以前的研究表明，适度的咖啡因给药保护/恢复AD转基因小鼠的认知功能，并抑制脑β-淀粉样蛋白（Aβ）的产生。在本研究中，我们报告了对年轻成年和老年AD转基因小鼠急性给予咖啡因可迅速降低脑间质液和血浆中的Aβ水平，而不影响Aβ消除。长期口服咖啡因治疗老年AD小鼠不仅可持续降低血浆Aβ，而且可降低海马和皮质中可溶性和沉积的Aβ。不考虑咖啡因治疗，血浆Aβ水平与脑Aβ水平或个体老年AD小鼠的认知表现无关。虽然在老年AD小鼠中，较高的血浆咖啡因水平与较低的血浆Aβ1-40水平密切相关，但血浆咖啡因水平也与认知能力无关。血浆咖啡因和茶碱水平密切相关-两者都与海马体中炎性细胞因子水平降低有关。我们的结论是双重的。首先，在几个AD转基因品系和年龄中，急性或慢性给予咖啡因可降低血浆和脑Aβ水平，表明咖啡因对AD具有治疗价值。第二，血浆Aβ水平不是老年AD小鼠脑Aβ水平/沉积或认知能力的准确指标。
Recent epidemiologic studies suggest that caffeine may be protective against Alzheimer’s Disease (AD). Supportive of this premise, our previous studies have shown that moderate caffeine administration protects/restores cognitive function and suppresses brain β-amyloid (Aβ) production in AD transgenic mice. In the present study, we report that acute caffeine administration to both young adult and aged AD transgenic mice rapidly reduces Aβ levels in both brain interstitial fluid and plasma without affecting Aβ elimination. Long-term oral caffeine treatment to aged AD mice provided not only sustained reductions in plasma Aβ, but also decreases in both soluble and deposited Aβ in hippocampus and cortex. Irrespective of caffeine treatment, plasma Aβ levels did not correlate with brain Aβ levels or with cognitive performance in individual aged AD mice. Although higher plasma caffeine levels were strongly associated with lower plasma Aβ1-40 levels in aged AD mice, plasma caffeine levels were also not linked to cognitive performance. Plasma caffeine and theophylline levels were tightly correlated — both being associated with reduced inflammatory cytokine levels in hippocampus. Our conclusion is two-fold. First, that both plasma and brain Aβ levels are reduced by acute or chronic caffeine administration in several AD transgenic lines and ages, indicating a therapeutic value of caffeine against AD. Second, that plasma Aβ levels are not an accurate index of brain Aβ levels/deposition or cognitive performance in aged AD mice.