Medicina molecular y genética

Inflammation, Immune System and Alzheimer's disease: A Review of the Findings from the Major GWAS Studies

Abstract

Reitz Christiane and Tosto Giuseppe

A role for inflammation in the pathogenesis of Alzheimer's disease (AD) has been a matter of debate since the beginning of AD research in 1907. Over the past three decades immunohistochemical studies demonstrated that amyloid plaques are co-localized with activated microgliaas well as a broad spectrum of inflammation-related proteins (complement factors, acute-phase proteins, pro-inflammatory cytokines) spurring the hypothesis that amyloid plaques may benests of a non-immune mediated inflammatory reactions induced by fibrillar Aβ deposits. However, molecular studies also suggest that inflammation-related proteins are involved in Aβ generation and clearance, gliosis and increased phosphorylation of tau with accelerated tangle formation, i.e. several events considered key pathogenic steps in AD. In line with both notions, neuropathological studies show a close relation between fibrillar Aβ deposits, inflammation and neuroregeneration in relatively early stages preceding extensive tau-related neurofibrillary changes. Genetic studies address the issue of reverse causation and thus can help clarify the temporal relation between inflammatory changes and AD. In this review article we summarize the findings on inflammatory genes from the large scale genetic studies in AD and discuss directions for future research.