A higher level of M2 markers (Arg-1, MRC1/CD206) and a lower level of classic M1 markers (TNFa, IL-1β) were obtained in Aβ-pretreated N9 cells with chitinase1, suggesting that chitinase1 polarized the microglia into an anti-AD M2 phenotype.
In the current report, we determined the effects of microRNA-155 (miR-155) on the levels of IL-1β, IL-6 and TNF-α, and their respective receptors in the hippocampus using a rat model of AD.
Because there is increasing interest in the common disruption of cytokine pathways seen in both AD and schizophrenia, we tested the association between the functional interleukin-1beta -511 promoter polymorphism with delusions and hallucinations in AD.
Most genes conferring susceptibility to AD are related to amyloid-beta deposition (APP; PS1; PS2; APOE; Cystatin-C; ubiquilin-1), oxidative stress (NOS2; NOS3) and inflammatory response (IL-1 alpha; IL-1 beta; IL-6; TNF-alpha).
Prostaglandins (PGs) and cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6), have been implicated in the etiopathology of various inflammatory and degenerative disorders, including Alzheimer's disease (AD).
These findings indicate that the IL-1β-511C/T polymorphism might be associated with AD risk, and individuals with IL-1β -511C/C genotype might be at higher risk of AD in non-Europe.
A number of genetic risk factors have been identified for Alzheimer's disease (AD) including genes involved in the inflammatory response (interleukin 1A, [IL-1α (-889)], interleukin 1B (IL-1β [+3953]), and tumor necrosis factor (TNF [-308 and -850]).
The triple transgenic mouse model of AD, which develops plaques and tangles later in its life cycle, was bred with IL-1β(XAT) mice, and effects of IL-1β overexpression on AD pathology were assessed in F1 progeny.
Inheritance of the IL-1alpha (-889) polymorphism (the T allele), previously shown to increase IL-1 production, has been associated with an elevated risk of Alzheimer's disease.
The accumulation of proinflammatory cytokines, such as IL1B (interleukin 1 β) and IL18 (interleukin 18), as well as the dysfunctional autophagy pathway may damage hippocampal neuronal cells, thus leading to hippocampal-dependent impairment in learning and memory, which is associated with the pathogenesis of Alzheimer disease (AD).
Importantly, CTSB activity, IL-1β levels and malondialdehyde (MDA) were remarkably elevated in plasma of AD patients compared to healthy controls, while glutathione was significantly lower than healthy controls.
As these patients are at higher risk of conversion to dementia, we propose that an increased serum IL-1beta level is a stage marker of the ongoing brain neurodegeneration in the continuum between normal ageing and AD.
Our findings suggest that IL-1beta gene by affecting brain immune responses may influence the age at onset of the disease, survival and AD progression.
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.
Multifunctional Compound AD-35 Improves Cognitive Impairment and Attenuates the Production of TNF-α and IL-1β in an Aβ25-35-induced Rat Model of Alzheimer's Disease.
Brain inflammation including increases in inflammatory cytokines such as IL-1β is widely believed to contribute to the pathophysiology of Alzheimer's disease.
TNF-α -308G/A and IL-8 -251T/A were significantly associated with AD and IL-1β+3953C/T with late-life depression, while the significance of these associations was lost after Bonferroni correction.
Inflammasomes, which regulate IL-1β release, are formed following activation of cytosolic PRRs, and using genetic and pharmacological approaches, NLRP3 and NLRP1 inflammasomes have been found to be integral in pathogenic neuroinflammation in animal models of Alzheimer's disease.