IFN-γ and TNF-α Are Involved During Alzheimer Disease Progression and Correlate with Nitric Oxide Production: A Study in Algerian Patients

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease leading to a progressive and irreversible loss of mental functions. It is characterized by 3 stages according to the evolution and the severity of the symptoms. This disease is associated with an immune disorder, which appears with significant rise in the inflammatory cytokines and increased production of free radicals such as nitric oxide (NO). Our study aims to investigate interferon (IFN)-γ and tumor necrosis factor-α (TNF-α) involvement in NO production, in vivo and ex vivo, in peripheral blood mononuclear cells from Algerian patients (n=25), according to the different stages of the disease (mild Alzheimer's, moderate Alzheimer's, and severe Alzheimer's) in comparison to mild cognitive impairment (MCI) patients. Interestingly, we observed that in vivo IFN-γ and TNF-α levels assessed in patients with AD in mild and severe stages, respectively, are higher than those observed in patients with moderate stage and MCI. Our in vivo and ex vivo results show that NO production is related to the increased levels of IFN-γ and TNF-α, in mild and severe stages of AD. Remarkably, significant IFN-γ level is only detected in mild stage of AD. Our study suggests that NO production is IFN-γ dependent both in MCI and mild Alzheimer's patients. Further, high levels of NO are associated with an elevation of TNF-α levels in severe stage of AD. Collectively, our data indicate that the proinflammatory cytokine production seems, in part, to be involved in neurological deleterious effects observed during the development of AD through NO pathway.

The Role of 6-Gingerol on Inhibiting Amyloid β Protein-Induced Apoptosis in PC12 Cells

“…Studies have indicated that NO can generate a high level of pro-inflammatory cytokines to strengthen neurotoxicity, and this increase is consequently related to the development of AD. 26 Ab blocks the normally reparative effects of up-regulated vascular endothelial growth factor and nitric oxide synthases (NOS) and may accelerate in vivo vascular pathophysiology in AD. 27 Excessive NO generated by NOS could strengthen the neurotoxicity because of the inhibition of glutamate reuptake, hence contributing to neuronal death and injury.…”

The Role of Inflammatory Mediators in the Pathogenesis of Alzheimer’s Disease

“…Collectively, this suggests that NO production is IFN-γ-dependent in AD. 37 On the other hand, IFN-γ is a known inhibitor of APP fragment production. IFN-γ can prevent amyloid deposition during inflammatory processes in both non-neuronal and neuronal tissues.…”

“…5 Importantly, Belkhelfa et al revealed recently that a high level of NO is associated with the rise of TNF-α levels in patients in the severe stages of AD. 37 In response to numerous intrinsic and extrinsic stimuli, TNF-α is produced by microglia, astrocytes and neurons in the brain. In addition, genetic and epidemiological findings have implicated augmented levels of TNF-α in the brain as a risk factor for AD.…”

“…In addition, genetic and epidemiological findings have implicated augmented levels of TNF-α in the brain as a risk factor for AD. 37 TNF-α can mediate neuronal dysfunction as well as Aβ-induced disruption of the molecular mechanisms involved in memory function. Likewise, TNF-α can stimulate accumulation of the tau proteins in neurites through induction of ROS.…”

Serum Anticholinergic Activity as an Index of Anticholinergic Activity Load in Alzheimer's Disease

“…The reason why changes of AA in the CNS link with that of SAA is considered to be the following: SAA inhibits muscarinic ACh activity of parasympathetic neurons and produces cytokine activation with macrophages; then, the proinflammatory cytokines penetrate into the brain and possibly activate the microglia. The activated microglia in the brain produces proinflammatory cytokines accelerating AD [16,18,19]. Therefore, any AA produced in the brain or peripheral tissue causes inflammation activating microglia or macrophages, respectively; the produced proinflammatory cytokines penetrate the BBB both ways, and then the AA reflects each region.…”