Neuroinflammatory perspectives on the two faces of Alzheimer's disease.

The amyloid plaques in Alzheimer's disease (AD) brains are co-localized with a broad variety of inflammation-related proteins (complement factors, acute-phase proteins, pro-inflammatory cytokines) and clusters of activated microglia. The present data suggest that Abeta deposits in AD brains are closely associated with a locally induced, non-immune mediated, chronic inflammatory response. Clinicopathological and neuroradiological studies show that activation of microglia is a relatively early pathogenic event that precedes the process of neuropil destruction in AD. Epidemiological studies indicate that polymorphisms of certain cytokines and acute-phase proteins that are colocalized with Abeta plaques, are genetic risk factors of AD. Epidemiological studies have also shown that the use of classical nonsteroidal anti-inflammatory drugs (NSAIDs) can prevent the risk of AD but clinical trials with anti-inflammatory drugs in AD patients were negative. These findings indicate that anti-inflammatory agents can be helpful in the prevention but not in the treatment of AD. So, pathological, genetic and therapeutic studies suggest that inflammatory mechanisms are most likely involved in the early steps of the pathological cascade. In the autosomal dominant inherited forms of AD the primary factor is the increased production of Abeta1-42 resulting into fibrillar Abeta deposition that elicits a brain inflammatory response. The etiology of the sporadic forms is yet unknown but this subtype is considered to be heterogeneous and multifactorial in its pathogenesis. Here we review the evidence that inflammation related events could be a critical etiological factor in certain forms of the sporadic AD.