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.

Comorbidities in Neurology: Is adenosine the common link?

“…Mechanisms contributing to the loss of astrocyte-mediated neuroprotective functions, as well as to astrocyte-mediated neurotoxicity have been reported in ALS (Lepore et al, 2008; Martorana et al, 2012a). Accordingly, a subpopulation of spinal cord astrocytes has been shown to degenerate in ALS and impaired astrocytic functions, such as clearance of extracellular glutamate have been described (Lasiene and Yamanaka, 2011; Martorana et al, 2012b; Neusch et al, 2007).…”

A Perspective on Roles Played by Innate and Adaptive Immunity in the Pathobiology of Neurodegenerative Disorders

“…Pathologically clinical neurological features are associated by deposition of extracellular amyloid-beta protein (Aβ) and the formation of neurofibrillary tangles (Lashley et al, 2015). Immunosenescence and inflammation contributes to AD pathogenesis (Candore et al, 2010; Di Bona et al, 2010; Martorana et al, 2012; Michaud et al, 2013; Castelo-Branco and Soveral, 2014; Fulop et al, 2015). Systemic immunity affects disease pathogenesis by altering the phenotype of microglia (Heneka et al, 2015; Latta et al, 2015; Lucke-Wold et al, 2015; Mhatre et al, 2015; Yamada, 2015; Zhang and Jiang, 2015).…”

Alzheimer's disease vaccine development: A new strategy focusing on immune modulation

“…While it has been assumed that because of the BBB the CNS is an immunologically privileged site, actually the BBB is like a regulatory interface between the CNS and the immune system that can selectively transport certain cytokines and secrete neuroinflammatory compounds (Martorana et al, 2012;Erickson et al, 2012). Hence, it is possible to assume that an inflammatory immune response occurring outside the CNS, may affect it indirectly by inducing the BBB to secrete neuroinflammatory substances into the CNS (Erickson et al, 2012); which may aggravate the course of neurodegenerative diseases.…”

“…Because Th1 adjuvants are very effective, it has been suggested to use them to induce inflammatory cytokines and enhance vaccines' efficacy in the elderly (Haynes et al, 2004). Yet, regardless of the absence of T-cell epitopes in an immunogen, Th1 adjuvants would induce a systemic immunity that spreads throughout the body via cytokines; which may be transported across the blood-brain barrier (BBB) to stimulate an inflammatory response in the central nervous system (CNS) (Martorana et al, 2012). A concern with Aβ is its intrinsic capacity to stimulate in vivo Th1 immunity and increase in vitro the production of inflammatory cytokines by dendritic cells (DC) (Szczepanik et al, 2001;Vollmar et al, 2010).…”

“…Another hindrance to the development of AD vaccines is immunosenescence (Martorana et al, 2012). While strong immunity can be readily achieve upon vaccination in the younger population, it is difficult to get such immunoresponse in the aging one, target of the AD vaccine.…”