Neuroinflammation Is a Prominent Feature of Alzheimer's Disease

Researchers are increasingly considering chronic, unresolved inflammation in brain tissue to be an important pathological mechanism in Alzheimer's disease. Removing senescent cells from the brain has reduced pathology in mouse models of Alzheimer's disease. While, as ever, the issue with all such models is their artificiality, as mice do not naturally suffer anything resembling Alzheimer's disease, it is well established that inflammation is a feature of Alzheimer's disease in humans. We have a good idea as to the major causes of this inflammation: senescent cells, an altered gut microbiome, debris from stressed cells that provokes an innate immune reaction, and so forth. Targeting the causes of excessive inflammation without suppressing the whole immune response may well prove to be a useful preventative treatment for many age-related conditions.

Alzheimer's disease (AD) should be viewed as a systemic disease that involves dynamic processes in the peripheral and central immune compartments. The conceptualization of the pathogenesis of AD remains elusive, with many competing hypotheses, particularly those based on proteopathic and immunopathic mechanisms. The peripheral and central immune systems are dysregulated in AD and are related to the cognitive function and clinical status. They may change in a non-linear manner over time, and burgeoning evidence also suggests that the roles of the innate and adaptive immune processes differ depending on the pathological stage of AD.

Animal studies have provided insights into the possible mechanisms of peripheral and central immune communication, including direct pathways that involve peripheral immune cell infiltration of the central nervous system (CNS), as well as indirect pathways that involve the systemic-inflammation-driven modulation of the microglial function. The possibility of the involvement of other processes, such as the immune system, in AD remains underexplored, even though many immune mechanisms, such as phagocytosis, aid in the reduction in AD pathologies and, on the contrary, the dysfunction of the immune system has largely been painted as detrimental to the AD pathology. Recently, there has been increasing interest in the role of the immune system in neurodegeneration due to the accumulating evidence stressing the role of the immune system as an essential factor or a major driver of neuroinflammation processes, Alzheimer's pathogenesis and AD progression. In fact, immunosenescence is a dysregulation of the immune system that accompanies aging.

Immunotherapies and neuroimmune manipulations, which can treat a wide array of diseases, can effectively treat the disease and the changes it makes to our body's watchdog, the immune system. Moreover, the suppression of inflammatory cytokines has been seen to be beneficial in immunomodulation. In order to fight neuroinflammation under chronic neurodegenerative conditions, systemic immunity should be boosted rather than suppressed. Thus, we stress the idea that, in efforts to fight AD, it might be possible to target the immune system rather than directly target specific disease-escalating factors within the brain. The rebalancing of the immune response and its exploitation to wipe toxic plaques from the brain may bring new hope for a safe and effective treatment for this devastating illness.


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