Role of neuroinflammation in neurodegeneration: new insights

Previously, the contribution of peripheral infection to cognitive decline was largely overlooked however, the past 15 years have established a key role for infectious pathogens in the progression of age-related neurodegeneration. It is now accepted that the immune privilege of the brain is not absolute, and that cells of the central nervous system are sensitive to both the inflammatory events occurring in the periphery and to the infiltration of peripheral immune cells. This is particularly relevant for the progression of Alzheimer’s disease, in which it has been demonstrated that patients are more vulnerable to infection-related cognitive changes. This can occur from typical infectious challenges such as respiratory tract infections, although a number of specific viral, bacterial, and fungal pathogens have also been associated with the development of the disease. To date, it is not clear whether these microorganisms are directly related to Alzheimer’s disease progression or if they are opportune pathogens that easily colonize those with dementia and exacerbate the ongoing inflammation observed in these individuals. This review will discuss the impact of each of these challenges, and examine the changes known to occur with age in the peripheral immune system, which may contribute to the age-related vulnerability to infection-induced cognitive decline

Inflammaging decreases adaptive and innate immune responses in mice and humans

Both the innate and adaptive immune systems decline with age, causing greater susceptibility to infectious diseases and reduced responses to vaccination. Diseases are more severe in elderly than in young individuals and have a greater impact on health outcomes such as morbidity, disability and mortality. Aging is characterized by increased low-grade chronic inflammation, called “inflammaging”, measured by circulating levels of TNF-α, IL-6 and CRP, as well as by latent infections with viruses such as cytomegalovirus (CMV). Inflammaging has received considerable attention because it proposes a link between changes in immune cells and a number of diseases and syndromes typical of old age. In this review we aim at summarizing the current knowledge on pathways contributing to inflammaging, on immune responses down-regulated by inflammation and mechanisms proposed. The defects in the immune response of elderly individuals presented in this review should help to discover avenues for effective intervention to promote healthy aging