EVALUATION OF HOW CIGARETTE SMOKE IS A DIRECT RISK FACTOR FOR ALZHEIMER'S DISEASE.
EVALUATION OF HOW CIGARETTE SMOKE IS A DIRECT RISK FACTOR FOR ALZHEIMER'S DISEASE.
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DOI：
10.3727/194982412x13378627621752
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发表时间：
2012-01-01
影响因子：
0.5
通讯作者：
Tan J
中科院分区：
文献类型：
--
作者：
Giunta B;Deng J;Jin J;Sadic E;Rum S;Zhou H;Sanberg P;Tan J
吸烟有患阿尔茨海默病（AD）的风险，AD的病理标志是淀粉样蛋白-β (a β)脑沉积。我们发现中度吸烟者的AD调整风险显著增加（RR = 2.56; 95% CI = 1.65-5.52），重度吸烟者的风险更高（RR = 3.03; 95% CI = 1.25-4.02）。这一系统综述和原始数据进一步支持了这一关联。我们检索了Pubmed、b谷歌scholar和PsyINFO，检索了1987年至2011年间发表的原始人口研究文章、元分析和评论。一些研究因设计缺陷（包括幸存者偏差）而被排除。我们分析了：1)暴露于香烟烟雾冷凝物（CSC）中过表达瑞典突变体APP （SweAPP N2a）的N2a细胞的淀粉样前体蛋白（APP）加工，2)对CSC的小胶质炎症反应，以及3)CSC暴露于Aβ1-42的小胶质吞噬。CSC显著促进神经元Aβ的生成，增加小胶质细胞IL-1β和TNF-α的产生，减少小胶质细胞Aβ1 - 42的吞噬。吸烟与AD的流行病学关联的潜在机制可能涉及吸烟对APP加工的影响，小胶质细胞对a β清除的减少，和/或小胶质细胞促炎反应的增加。需要进行体内研究来充分阐明吸烟是如何促进AD的。
Cigarette smoking is a risk for Alzheimer’s disease (AD), the pathological hallmark of which is amyloid-β (Aβ) brain deposits. We found the adjusted risk of AD was significantly increased among medium level smokers (RR = 2.56; 95% CI = 1.65–5.52), with an even higher risk in the heavy smoking group (RR = 3.03; 95% CI = 1.25–4.02). This systematic review and original data further support this association. We searched Pubmed, Google scholar, and PsyINFO for original population study articles, meta-analyses, and reviews published between 1987 and 2011. Some studies were excluded due to design flaws including survivor bias. We performed analyses of: 1) amyloid precursor protein (APP) processing in N2a cells overexpressing Swedish mutant APP (SweAPP N2a) exposed to cigarette smoke condensate (CSC), 2) microglial inflammatory response to CSC, and 3) CSC exposed microglial phagocytosis of Aβ1–42. CSC significantly promotes neuronal Aβ generation, increases microglial IL-1β and TNF-α production, and decreases microglial Aβ1–42 phagocytosis. The mechanism underlying the epidemiological association of cigarette smoking with AD might involve the effect of cigarette smoke on APP processing, a reduction of Aβ clearance by microglia, and/or an increased microglial proinflammatory response. In vivo studies are required to fully elucidate how cigarette smoke promotes AD.