These results suggest that the cerebral microcirculation contributes proinflammatory cytokines to the milieu of the AD brain and may be involved in the pathogenesis of neuronal injury and death in this disorder. In addition, several studies 48 , 49 suggest that sustained inflammation from the periphery can cause pro-inflammatory cytokines in the CNS by crossing the blood-brain barrier BBB and can contribute to cognitive decline in AD patients. Indeed, Capuron and Miller 50 recently reviewed the pathways for the transport of pro-inflammatory cytokines to brain from systemic circulation. Based on these findings, one can envisage that brain pro-inflammatory cytokines may be considered as a biomarker of AD.
Frontiers | Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines | Immunology
Thus, it seems that any significant inflammatory response within the brain tissue will be associated with pro-inflammatory cytokines dysfunction, raising the potential use of pro-inflammatory cytokines measure as a surrogate marker for a local inflammatory response in AD. Altered levels of biomarkers in CSF are supported to be active long before the symptoms appear; moreover the CSF near to the brain parenchyma and the extracellular fluid of the brain.
Recently, the occurrence of a plaque-dependent inflammation in AD has been extensively documented. There is intense interest in the use of proinflammatory cytokines as biomarkers of AD because they are upregulated during the earliest, oligomeric-induced inflammatory process in AD brains. The deregulation of several pro-inflammatory cytokines has been demonstrated implicated in the pathogenesis of AD.
McAlpine et al. Their biological effects are differentially expressed and regulated. Moreover, McAlpine et al. Recently, Montgomery et al. For example, As early as , Barger et al. Moreover, Tarkowski et al. Recently, Parajuli et al. Some studies have suggested that these two factors participate in a vicious cytokine cycle that once induced and derived AD pathology Figure 4. IL-6 is a pleiotropic inflammatory cytokine mainly produced by activated microglia, astrocytes in different brain regions.
In addition, IL-6 could stimulate microglia and astrocytes to release a cascade of proinflammatory cytokines and acute-phase proteins, such as C-reactive protein CRP The levels of IL-6 have been found significantly elevating in the brains, cerebrospinal fluid, and plasma, especially locally around amyloid plaques in AD patients and animal models. Therefore, it has been proposed IL-6 is involved in the etiopathology of AD with acute or chronic inflammatory components. Firstly, studies clearly demonstrated the role of IL-6 that contribute to APP processing and production in primary rat cortical neurons IL-6 in neuroinflammation and neurodegeneration also plays a complex role in regulating cognitive function As early as , Weaver et al.
Subsequently, many researchers confirmed that under inflammatory conditions, excessive IL-6 through activation of neuronal NADPH-oxidase induced by aging or inflammation may impair cognitive processes, such as spatial learning and memory Activated microglia, astrocytes and ependymal cells and neurons in the CNS are all the source of IL Recently, accumulating date demonstrated that IL may involve in the different aspects of neurodegeneration in AD.
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Basis for Binding of Type I Cytokines to Their Receptors
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