Involvement of inflammation in Alzheimer’s disease pathogenesis and therapeutic potential of anti-inflammatory agents

Abstract

Alzheimer's disease (AD) is the most common form of dementia. It is characterized by beta-amyloid (Aβ) peptide fibrils, which are extracellular depositions of a specific protein, and is accompanied by extensive neuroinflammation. Various studies have demonstrated risk factors that can affect AD pathogenesis, and they include accumulation of Aβ, hyperphosphorylation of tau protein, and neuroinflammation. Among these detrimental factors, neuroinflammation has been highlighted by epidemiologic studies suggesting that use of anti-inflammatory drugs could significantly reduce the incidence of AD. Evidence suggests that astrocytes, microglia, and infiltrating immune cells from periphery might contribute to or modify the process of neuroinflammation and neurodegeneration in AD brains. In addition, recent data indicate that microRNAs may affect neuroinflammatory responses in the brain. This article focuses on supportive evidence that neuroinflammation plays a critical role in AD development. In addition, we depict putative therapeutic capacity of anti-inflammatory drugs for AD prevention or treatment. We also discuss pathogenic mechanisms by which astrocytes, microglia, T cells and microRNA participate in AD and the neuroprotective mechanisms of anti-inflammatory drugs.

An Extract from Shrimp Processing By-Products Protects SH-SY5Y Cells from Neurotoxicity Induced by Aβ25–35

“…Experimental and clinical findings provide evidence for the hypothesis that the neuronal degeneration in AD is not simply due to the Aβ deposition, but to neuroinflammation [45,46]. Consistent with the above studies, an increased expression of TNF-α gene was found in the present AD cellular model.…”

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

“…Indeed, there is an ever-expanding pool of data from both human studies and animal models of AD that highlights the crucial role played by neuroinflammation in AD. For recent reviews of the literature in this field, the reader is directed to the following comprehensive articles (Heneka et al, 2015;Heppner et al, 2015;McGeer and McGeer, 2013;Shadfar et al, 2015). Epidemiological and clinical studies in human AD patients have provided some interesting perspectives on neuroinflammation and in some cases have stimulated further work in animal models of the disease.…”

BHBA treatment improves cognitive function by targeting pleiotropic mechanisms in transgenic mouse model of Alzheimer's disease

“…[36][37][38] On the other hand, the microglia had been shown to play an important role in synaptic formation and plasticity during brain development. 47,48 We found increased microglia accumulation and expression of inflammatory cytokines in the cortex or the hippocampus in 5XFAD mice compared with WT mice, while BHBA treatment significantly attenuated neuro-inflammation. 41,42 Furthermore, activated microglia express pro-inflammatory enzymes (iNOS and COX-2) and cytokines (TNF-α, IL-1β, and IL-6), 43 which may mediate neuronal degeneration, 44,45 Using mass spectrometry with bioinformatic analysis, Antonio et al found activation of JAK/STAT, p38 MAPK, and interleukin pathways in microglial cells of 5XFAD mice, indicating that innate immune alterations are elicited in microglial cells before plaque deposition in the AD mouse model.…”