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

Abstract

Currently, there is little doubt that the immune system plays a role in the neurodegenerative process in Alzheimer's disease (AD). Inflammatory proteins such as complement components, enzymes, eicosanoids, and cytokines are found in association with cerebral amyloid plaques and may exacerbate the fundamental pathology of AD, by stimulating Amyloid beta (A beta) production, supporting its aggregation and increasing its cytotoxicity. Activated microglia and astrocytes are the main source of these proteins, and A beta may trigger their release. Interestingly, there are also indications that the immune system may play a protective role against the development of AD. Microglial cells have been shown to degrade A beta, and recent evidence suggests that autoreactive A beta-specific T cells may be relevant to the elimination of the peptide. This mechanism seems, however, impaired in the majority of patients with AD. The immune system seems thus to represent a natural line of defense against the accumulation of dangerous amyloidogenic substances. Impairment of this specific immunological defense mechanism and the failure to eliminate a toxic metabolite can be the basis for a chronic nonspecific inflammatory process in the brain, as described above. AD is a good example how an immune response initially aiming at maintaining the integrity of the body may fail and consequently lead to tissue destruction and neuronal loss.