The Importance of Inflammation in Alzheimer's Disease
Continual, unresolved inflammation is a feature of all of the common age-related conditions, and particularly so in the brain. When sustained for the long-term, inflammatory signaling is disruptive to tissue structure and function, and thus contributes to dysfunction and eventual mortality. Here, researchers focus on the role of the chronic inflammation of aging in Alzheimer's disease specifically, though most of what is said can be applied to the etiology of other neurodegenerative conditions as well.
Alzheimer's disease (AD) is an age-related neurodegenerative disorder and the most common cause of dementia. While the amyloid cascade hypothesis has long dominated AD research, emerging evidence suggests that neuroinflammation may play a more central role in disease onset and progression. Increasingly, AD is recognized as a multifactorial disorder influenced by systemic inflammation and immune dysregulation, shifting focus toward peripheral immune mechanisms as potential contributors to neurodegeneration.
This review explores the hypothesis that inflammaging, the age-related increase in pro-inflammatory mediators, combined with lifelong exposure to infections, injuries, metabolic changes, and chronic diseases, among others, may prime the immune system, amplifying neuroinflammation and influencing the progression and exacerbation of AD pathology. To this end, we examined how systemic immune disturbances, including chronic pain, post-operative cognitive dysfunction, viral and bacterial infections, gut microbiome dysregulation, and cardiovascular disease, may act as risk factors for AD. Overall, evidence suggests that modulating peripheral inflammation, accompanied by early diagnosis, could significantly reduce the risk of developing AD.
Furthermore, we highlight key immune signaling pathways involved in both central and peripheral immune responses, such as the NLRP3 inflammasome and TREM2, which represent promising therapeutic targets for modulating inflammation while preserving protective immune functions. Strategies aimed at reducing systemic inflammation, identifying early biomarkers, and intervening before significant neurodegeneration occurs may provide novel approaches to delay or prevent AD onset.