Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging
Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging
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DOI：
10.1212/wnl.50.4.986
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发表时间：
1998-04-01
期刊：
影响因子：
9.9
通讯作者：
Munoz, DG
中科院分区：
文献类型：
--
作者：
Mackenzie, IRA;Munoz, DG
抗炎药物被认为是治疗阿尔茨海默病（AD）的一种可能的方法。在AD和正常衰老中，免疫蛋白和免疫能力小胶质细胞与老年斑（SP）的关联表明，这些药物可能能够通过干扰SP的形成或抑制与SP相关的炎症来改变AD的病程。我们比较了有慢性非甾体抗炎药（NSAID）使用史的老年、非痴呆、关节炎患者的死后脑组织（n = 32）。年龄77 +/- 7岁)和无关节炎史或其他可能促进非甾体抗炎药常规使用的疾病的非痴呆对照组（n = 34，年龄77 +/- 6岁）。在非甾体抗炎药治疗组和对照组中，59%的患者有一定程度的SP。两组之间在平均斑块数量或特定SP亚型（弥漫性或神经性）数量上没有差异。神经原纤维病变程度也相似。使用抗mhc II类抗体CR3/43鉴定活化的小胶质细胞。患者年龄和SP的存在与CR3/43+小胶质细胞数量呈正相关（p < 0.02），而使用非甾体抗炎药与小胶质细胞激活减少相关（p < 0.01）。对照组SP患者激活的小胶质细胞数量几乎是nsaid治疗SP患者的3倍（11个细胞/mm vs 4个细胞/mm(2), p < 0.02）。这些结果表明，如果使用非甾体抗炎药治疗AD有效，其机制更可能是通过抑制小胶质细胞活性，而不是抑制SP或神经原纤维缠结的形成。
Anti-inflammatory drugs have been suggested as a possible treatment for Alzheimer's disease (AD). The association of immune proteins and immune-competent microglial cells with senile plaques (SP) in both AD and normal aging suggests that these drugs may be able to modify the course of AD, either by interfering with SP formation or by suppressing the inflammation associated with SP. We compared postmortem brain tissue from elderly, nondemented, arthritic patients with a history of chronic nonsteroidal anti-inflammatory drug (NSAID) use (n = 32, aged 77 +/- 7 years) and nondemented control subjects with no history of arthritis or other condition that might promote the regular use of NSAIDs (n = 34, aged 77 +/- 6 years). In both the NSAID-treated group and control subjects, 59% of patients had some SP. There was no difference between the two groups in the mean number of plaques or in the number of specific SP subtypes (diffuse or neuritic). The degree of neurofibrillary pathology was also similar. Activated microglia were identified using CR3/43, an anti-MHC class II antibody. Both patient age and the presence of SP correlated positively with the number of CR3/43+ microglia (p < 0.02), whereas NSAID use was associated with less microglial activation (p < 0.01). Control patients with SP had almost three times the number of activated microglia as NSAID-treated patients with SP (11 versus 4 cells/mm(2), p < 0.02). These results suggest that if NSAID use is effective in treating AD, the mechanism is more likely to be through the suppression of microglial activity than by inhibiting the formation of SP or neurofibrillary tangles.