MINIREVIEW - THE IMPORTANCE OF INFLAMMATORY MECHANISMS IN ALZHEIMER-DISEASE

Lesions in such chronic neurodegenerative disorders as Alzheimer disea se (AD), Parkinson disease, the parkinsonism dementia complex of Guam, and amyotrophic lateral sclerosis have associated with them a variety of proteins known to be involved in inflammatory processes. This is p articularly true of AD, where inflammatory reactions are thought to be important contributors to the neuronal loss. Proteins present include complement proteins, complement inhibitors, acute phase reactants, in flammatory cytokines, proteases, and protease inhibitors. Studies of c ultured human astrocytes and microglia, obtained from postmortem brain , have established that nearly all of these proteins are produced by o ne or another of these cell types. Human neurons also produce many inf lammatory proteins and their inhibitors, creating complex interactions . Accumulations of amyloid and extracellular tangles apparently act as irritants, causing the activation of complement, the initiation of re active changes in microglia, and the release of potentially neurotoxic products. Such products include the membrane attack complex, oxygen f ree radicals, and excess glutamate. Twenty epidemiological studies tha t have been published to date indicate that populations taking antiinf lammatory drugs have a significantly reduced prevalence of AD or a slo wer mental decline. One small clinical trial with indomethacin showed arrest of the disease over a six-month period. Therapeutic interventio n in key inflammatory processes holds great promise for the ameliorati on of AD and possibly other neurodegenerative disorders. (C) 1998 Else vier Science Inc.