Alzheimer’s disease (AD) is a neurodegenerative disease associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise with increasing age. There are currently no effective disease modifying treatments for AD, resulting in increasingly large socioeconomic and personal costs. Increasing age is associated with an increase in low-grade chronic inflammation (inflammaging) that may contribute to the neurodegenerative process in AD. Although the exact mechanisms remain unclear, aberrant elevation of reactive oxygen and nitrogen species (RONS) levels from several endogenous and exogenous processes in the brain may not only affect cell signaling, but also trigger cellular senescence, inflammation, and pyroptosis. Moreover, a compromised immune privilege of the brain that allows the infiltration of peripheral immune cells and infectious agents may play a role. Additionally, meta-inflammation as well as gut microbiota dysbiosis may drive the neuroinflammatory process. Considering that inflammatory/immune pathways are dysregulated in parallel with cognitive dysfunction in AD, elucidating the relationship between the central nervous system and the immune system may facilitate the development of a safe and effective therapy for AD. We discuss some current ideas on processes in inflammaging that appear to drive the neurodegenerative process in AD and summarize details on a few immunomodulatory strategies being developed to selectively target the detrimental aspects of neuroinflammation without affecting defense mechanisms against pathogens and tissue damage.
Background Astrocytes are specialized glial cells that when exposed to inflammatory factors go through a process known as reactive astrogliosis. Reactive astrocytes are a neuropathological feature of Alzheimer’s disease (AD). The etiology of AD is often explained by the accumulation of β‐amyloid peptides, a proteolytic product of the amyloid precursor protein (APP). However, inflammation also plays a prominent role in the development of AD. How reactive astrocytesparticipate in the pathogenesis of AD remains poorly understood Method To elucidate the role of astrocytes in the pathogenesis of AD we exploited different in vitro and in vivo models to investigate the role of Amyloid Precursor protein in setting the immune response of astrocytes. Result Our results show that overexpression of APP in human cortical astrocytes induces reactive phenotype, similar to astrocytes found in brains of AD patients. These reactive astrocytes produce significantly increased levels of INF‐g in comparison with control astrocytes. Similar positive correlation between APP levels and INF‐g is found also in astrocytes from AD transgenic and traumatic brain injury mice models. Conclusion Our data indicate that astrocytes are activated by high levels of APP, which promotes production and secretion of interferons and recapitulates salient features of astrocytes in AD.
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