Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms

Abstract

Neuroinflammatory processes are a central feature of Alzheimer's disease (AD) in which microglia are over-activated, resulting in the increased production of proinflammatory cytokines. Moreover, deficiencies in the antiinflammatory system may also contribute to neuroinflammation. Recently, advanced methods for the analysis of genetic polymorphisms have further supported the relationship between neuroinflammatory factors and AD risk because a series of polymorphisms in inflammation-related genes have been shown to be associated with AD. In this review, we summarize the polymorphisms of both pro-and anti-inflammatory cytokines related to AD, primarily interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha, IL-4, IL-10, and transforming growth factor beta, as well as their functional activity in AD pathology. Exploration of the relationship between inflammatory cytokine polymorphisms and AD risk may facilitate our understanding of AD pathogenesis and contribute to improved treatment strategies.

Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats

“…It has been reported that PICs are involved in alterations of cellular damage related to development of AD and significant increases in IL-1 β, IL-6 and TNF-α in the brain were observed following αβ 1-42 injection [33]. Consistent with the previous results, our present data further demonstrated that AD induces increasing levels of IL-1β, IL-6 and TNF-α in the hippocampal tissues.…”

“…Whereas inhibition of the enzymatic activity of Caspase-3 likely provides a mechanism to attenuate the cellular apoptosis, our data suggests a beneficial role played by activation of mTOR. Elevated levels of PICs in the hippocampal tissues are associated with increased disease vulnerability and AD-related pathological changes such as cell death [33]. Our data also showed that inhibition of mTOR increases upregulation of IL-6 and TNF-α in AD rats, but not IL-1β.…”

Polysaccharides from Ganoderma lucidum attenuate microglia-mediated neuroinflammation and modulate microglial phagocytosis and behavioural response

“…The expressions of IL-1β, IL-6 and iNOS are associated with neurodegenerative diseases. The IL-1β is a potent neuroimmune mediator that takes effect on various cell types including neurons and microglia [38]; iNOS expression is elevated in activated microglia with its synthetic product nitric oxide being one of the major causes of neurodegenerative diseases [39]; and the expression of IL-6 is also strongly linked to AD as an inflammatory mediator [40, 41]. These results thus provide implications that GLP might exhibit neuroinflammation modulatory effects in neurodegenerative diseases such as AD.…”

Microglial NLRP3 Activity in Alzheimer's Disease

“…Thus, a therapeutic approach targeting that 5′-flanking rs2027432 polymorphism is strongly associated with late-onset AD in Chinese population [33]. In a meta-analysis study, Di Bona and coworkers show that the IL1B +3953 TT genotype is associated with increased AD risk, while IL1B -511 TT genotype only increases AD risk in Caucasians [34]. Furthermore, studies demonstrate that mutations in the IL-18 gene are also associated with the development of AD.…”