A growing faction within the research community has come to view chronic inflammation as one of the most important mechanisms that contribute to degenerative aging. It is certainly the case that in the Alzheimer's field the evidence of recent years points toward inflammation as the major mediating mechanism linking the diverse pathologies of this neurodegenerative condition.
In today's open access paper, researchers put forward their view of the connections between inflammatory disease outside the brain and inflammatory disease inside the brain. They contribute to one another, creating an accelerating downward spiral of damage and dysfunction. This isn't a novel concept, but rather the usual perception of the way in which interactions between systems in the body cause aging to accelerate over time.
There are plenty of examples when it comes to organ damage leading brain damage. Brain function depends on correct kidney function, the provision of metabolites and filtering of waste products, and thus chronic kidney disease contributes strongly to the progression of dementia. Similarly, the brain is injured by cardiovascular aging in a number of ways: hypertension resulting from stiffness of blood vessels causes rupture of capillaries and consequent cell death; heart failure reduces the supply of oxygen and nutrients; and so forth.
Chronic neuroinflammation is well accepted as the most relevant pathological features of AD, regulating other pathological hallmarks of Alzheimer's disease (AD), such as the accumulation of amyloid-β (Aβ) and hyperphosphorylation of Tau, both of which are involved in the neuronal dysfunction in AD. However, there is a great deal of evidence suggesting the important role of systemic inflammation in the pathogenesis of AD, especially in neuroinflammation.
There is increasing evidence suggesting that chronic neuroinflammation, and indeed inflammation in general, is the most relevant pathological feature of Alzheimer's disease (AD), regulating other pathological features, such as the accumulation of amyloid-β (Aβ) and hyperphosphorylation of Tau. Therapies aimed at reducing systemic inflammation in individuals with mild cognitive impairment (MCI) and AD have proven beneficial by delaying the cognitive decline in these individuals, suggesting that recognition of the cross-talk between systemic inflammation and neuroinflammation has important implications for AD therapeutic strategies.
It is well accepted that the pro-inflammatory mediators, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, are co-related factors involved in both systemic inflammation and neuroinflammation and affecting their sustainment and convergence. In contrast, intracellular enzymes, such as lysosomal cathepsins, mediate the production of pro-inflammatory mediators from both the periphery and brain.
Systemic inflammatory signals caused by systemic disorders are known to strongly influence neuroinflammation as a consequence of microglial activation, inflammatory mediator production, and the recruitment of peripheral immune cells to the brain, resulting in neuronal dysfunction. However, the neuroinflammation-accelerated neuronal dysfunction in AD also influences the functions of peripheral organs.
In the present review, we highlight the link between systemic inflammatory disorders and AD, with inflammation serving as the common explosion. We discuss the molecular mechanisms that govern the crosstalk between systemic inflammation and neuroinflammation. In our view, inflammation spreading indicates a negative spiral between systemic diseases and AD. Therefore, "dampening inflammation" may be a novel therapeutic approach for delaying the onset of and enacting early intervention for AD.