The possible role of the immune system in Alzheimer's disease

Currently, there is little doubt that the immune system plays a role in the neurodegenerative process in Alzheimer's disease (AD). Inflammatory protei ns such as complement components, enzymes, eicosanoids, and cytokines are f ound in association with cerebral amyloid plaques and may exacerbate the fu ndamental pathology of AD, by stimulating Amyloid beta (A beta) production, supporting its aggregation and increasing its cytotoxicity. Activated micr oglia and astrocytes are the main source of these proteins, and A beta may trigger their release. Interestingly, there are also indications that the i mmune system may play a protective role against the development of AD. Micr oglial cells have been shown to degrade A beta, and recent evidence suggest s that autoreactive A beta-specific T cells may be relevant to the eliminat ion of the peptide. This mechanism seems, however, impaired in the majority of patients with AD. The immune system seems thus to represent a natural l ine of defense against the accumulation of dangerous amyloidogenic substanc es. Impairment of this specific immunological defense mechanism and the fai lure to eliminate a toxic metabolite can be the basis for a chronic nonspec ific inflammatory process in the brain, as described above. AD is a good ex ample how an immune response initially aiming at maintaining the integrity of the body may fail and consequently lead to tissue destruction and neuson al loss. (C) 1998 Elsevier Science Inc.