Decline of Immune Responsiveness: A Pathogenetic Factor in Alzheimer’s Disease?

Abstract

While the etiopathogenesis of Alzheimer’s disease (AD) still remains unresolved, a growing body of evidence indicates the involvement of the immune system. Yet, both character and the significance of the observed alterations are matter of dispute. During the seventies and eighties of the 20th century a high amount of literature accumulated dealing with the impact of immunological factors on neurobehavioral pathology associated with aging and AD (Richartz et al. 2004). The putative relevance of inflammatory processes is shown by over 20 epidemiological studies suggesting a potential benefit of antiinflammatory intervention (Akiyama et al. 2000; McGeer and McGeer 1999). Further indication of a pathophysiological role of inflammation in AD is given by the presence of inflammatory mediators in the AD brain, including proinflammatory cytokines, acute phase proteins and the full complement cascade (Hull et al. 1996; Mrak et al. 1995; Tarkowski et al. 1999). In summary, data available suggest that the AD brain undergoes chronic inflammatory process mediated by activated glial cells, targeted on the destruction of senile plaques, but lethal to surrounding neurons (McGeer & McGeer 2003). The understanding that the brain is not that immunologically privileged site that it has been considered before is the result of modern psychoneuroimmunological research. There is an active and highly regulated communication between the Decline of Immune Responsiveness: A Pathogenetic Factor in Alzheimer’s Disease?