Immunosenescence, inflammation and Alzheimer's disease

Abstract

Ageing impacts negatively on the development of the immune system and its ability to fight pathogens. Progressive changes in the T-cell and B-cell systems over the lifespan of individuals have a major impact on the capacity to respond to immune challenges. The cumulative age-associated changes in immune competence are termed immunosenescence that is characterized by changes where adaptive immunity deteriorates, while innate immunity is largely conserved or even upregulated with age. On the other hand, ageing is also characterized by "inflamm-ageing", a term coined to explain the inflammation commonly present in many age-associated diseases. It is believed that immune inflammatory processes are relevant in Alzheimer's disease, the most common cause of dementia in older people. In the present paper we review data focusing on changes of some immunoinflammatory parameters observed in patients affected by Alzheimer's disease.

Keywords: Ageing; Alzheimer’s disease; Chemokine; Cytokine; Immunosenescence; Inflammation; Lymphocyte.

Figure 1

Communication between the central nervous system and systemic immune responses in Alzheimer’s disease patients. Inflammation clearly occurs in pathologically susceptible regions of the Alzheimer’s disease (AD) brain. Neurodegeneration and neuroinflammation can result in changes of central nervous system (CNS) proteins (for example, amyloid-beta (Aβ) peptide) or inflammatory mediators (acute-phase proteins and pro-inflammatory cytokines and chemokines) across the blood–brain-barrier (BBB). These CNS-derived proteins and mediators may induce systemic immune reactions and/or recruit lymphocytic cells into the CNS. The cells responsible for the inflammatory reaction in CNS are activated microglia and astrocytes. The hypothesis is that Aβ plaques and tangles stimulate a chronic inflammatory reaction. Other than CNS resident cells, blood-derived cells can also be blamed for inflammatory response and seem to accumulate in the AD brain due to the expression of chemokine receptors. The changes in lymphocyte distribution in the AD patient’s blood are also depicted.