Anti-inflammatory drugs: a hope for Alzheimer's disease?

Human brain cells are capable of initiating and amplifying a brain specific inflammatory response involving the synthesis of cytokines, acute-phase pr oteins, complement proteins, prostaglandins and oxygen radicals. In Alzheim er's disease (AD), all signs of an inflammatory microglial and astroglial a ctivation are present inside and outside amyloid depositions and along axon s of neurones with neurofibrillary tangles. Cell culture and animal models suggest a bidirectional relationship between inflammatory activation of gli al cells and the deposition of amyloid. Although it remains unclear which o f the different pathophysiological processes in AD may be the driving force in an individual case, the inflammatory activation may increase the speed of cognitive decline. Epidemiological studies point to a reduced risk of AD among users of anti-inflammatory drugs. Therefore, anti-inflammatory drugs have become the focus of several new treatment strategies. A clinical tria l with the non-steroidal anti-inflammatory drug (NSAID) indomethacin showed promising results, while a clinical trial with steroids did not show a ben eficial effect. Further trials with NSAIDs such as unselective cyclooxygena se (COX) and selective cyclooxygenase-2 (COX-2) inhibitors are on their way . COX inhibitors may not only act on microglial and astroglial cells but al so reduce neuronal prostaglandin production. New data suggest that prostagl andins enhance neurotoxicity or induce pro-inflammatory cytokine synthesis in astroglial cells. Amongst these promising new strategies to reduce micro glial or monocyte activation, interfering with intracellular pathways has b een shown to be effective in various cell culture and animal models but cli nical studies have not yet been performed.