Neuroinflammatory mechanisms are involved in the early steps of the pathological cascade in Alzheimer’s disease

Amyloid plaques in Alzheimer’s disease (AD) brains are closely associated with a locally induced, non-immune-mediated, chronic inflammatory response. Clinicopathological and neuroradiological studies have shown that activation of microglia is a relatively early pathogenic event that precedes the process of neuropil destruction in AD. Recent epidemiological studies have suggested that increased serum levels of some acute-phase reactants are associated with an increased risk of AD and that polymorphisms of certain cytokines, most notably interleukin-1, are genetic risk factors of AD. Epidemiological studies have also shown that the use of classical non-steroidal antiinflammatory drugs (NSAIDs) can prevent the risk of AD; however, clinical trials with antiinflammatory drugs have failed to arrest disease progression. These findings indicate that antiinflammatory drugs can be helpful in the prevention but not in the treatment of AD. Thus, pathological, genetic and pharmacoepidemiological studies suggest that inflammatory mechanisms are most likely to be involved in the early steps of the pathological cascade in AD.