Blain H, Jouzeau J Y, Blain A, Terlain B, Tréchot P, Touchon J, Netter P, Jeandel C
Service de Médicine interne-Gériatrie C, Centre de Gérontologie Médicale Antonin Balmes, CHU de Montpellier.
Presse Med. 2000 Feb 12;29(5):267-73.
Alzheimer's disease (AD) is a degenerative disease of the brain including possibly inflammatory mechanisms, as illustrated by the presence of activated microglial cells in the periphery of senile plaques and neurofibrillary tangles and the subsequent release of proinflammatory mediators with neurotoxic potency. RATIONALE FOR NSAID USE: Although not firmly demonstrated, the rationale for the prescription of non steroidal anti-inflammatory drugs (NSAIDS) as neuroprotective agents in AD lies on epidemiological data having shown a reduced risk of developing AD in patients on long-term therapy with NSAIDs (non selective cyclo-oxygenase [COX] inhibitors). RATIONALE FOR THE USE OF SELECTIVE COX-2 INHIBITORS: The rationale for the prescription of selective COX-2 inhibitors as neuroprotective drugs in AD lies on: Epidemiological data having shown a reduced risk of developing AD in patients treated with anti-inflammatory doses of classical NSAIDs (inhibition of COX-1 and COX-2) but not with antithrombotic doses of aspirin (selective inhibition of COX-1), Cellular experiments, Demonstration of a better gastro-intestinal (GI) safety profile with selective COX-2 inhibitors than with classical NSAIDs in short-term studies, allowing a possible long-term use in AD. BEFORE PRESCRIBING: COX-2 may have an ambivalent functionality in the brain since the basal production of prostaglandins through COX-2 may participate in neuronal homeostasis whereas the expression of COX-2 is associated with brain development. Classical NSAIDs are ineffective in reducing the formation of senile plaque and neurofibrillary tangles in AD, which is consistent with an ability to reduce inflammation associated with activation of microglia but illustrates their failure to suppress the degenerative process. Prophylactic use of selective COX-2 NSAIDs can be considered on the basis of their good GI safety after 6 months of marketing in United States but need to be confirmed for a longer time. CURRENT TRIALS: Clinical studies focusing on both the prevention and the slowing down of early AD are under way with two recently launched selective COX-2 inhibitors, celecoxib and rofecoxib.
阿尔茨海默病（AD）是一种脑部退行性疾病，可能涉及炎症机制，这一点可从老年斑和神经原纤维缠结周围活化的小胶质细胞的存在以及随后释放具有神经毒性的促炎介质得到证明。
非甾体抗炎药（NSAIDs）使用的理论依据：尽管尚未得到确凿证实，但将非甾体抗炎药作为AD的神经保护剂进行处方的理论依据在于流行病学数据表明，长期使用NSAIDs（非选择性环氧化酶[COX]抑制剂）治疗的患者患AD的风险降低。
选择性COX-2抑制剂使用的理论依据：将选择性COX-2抑制剂作为AD的神经保护药物进行处方的理论依据在于：流行病学数据表明，接受抗炎剂量的传统NSAIDs（抑制COX-1和COX-2）治疗的患者患AD的风险降低，但接受抗血栓剂量阿司匹林（选择性抑制COX-1）治疗的患者则不然；细胞实验；短期研究表明，选择性COX-2抑制剂的胃肠道（GI）安全性优于传统NSAIDs，这使得其有可能在AD中进行长期使用。
COX-2在大脑中可能具有矛盾的功能，因为通过COX-2产生前列腺素的基础过程可能参与神经元稳态，而COX-2的表达与大脑发育有关。传统NSAIDs在减少AD中淀粉样斑块和神经原纤维缠结的形成方面无效，这与它们减少与小胶质细胞活化相关的炎症的能力一致，但也说明了它们未能抑制退行性过程。在美国上市6个月后，基于其良好的胃肠道安全性，可以考虑预防性使用选择性COX-2 NSAIDs，但需要更长时间的证实。
目前正在进行两项针对早期AD预防和延缓的临床研究，使用两种最近推出的选择性COX-2抑制剂，塞来昔布和罗非昔布。
