Is Alzheimer disease a failure of mobilizing immune defense? Lessons from cognitively fit oldest-old.
Multifaceted evidence supports the hypothesis that inflammatory-immune mechanisms contribute to Alzheimer disease (AD) neuropathology and genetic association of several immune specific genes (TREM2, CR1, and CD33) suggests that maladaptive immune responses may be pivotal drivers of AD pathogenesis. We reviewed microglia-related data from postmortem AD studies and examined supporting evidence from AD animal models to answer the following questions: i) What is the temporal sequence of immune activation in AD progression and what is its impact on cognition? ii) Are there discordant, "primed", microglia responses in AD vs successful cognitive aging? iii) Does central nervous system (CNS) repair in aging depend on recruitment of the elements of cellular adaptive immune response such as effector T cells, and can the recruitment of systemic immune cells ameliorate AD neuropathology? iv) How effective are the immune-system-based therapeutic approaches currently employed for the treatment of AD?
['Katsel|Pavel|P|', 'Haroutunian|Vahram|V|']
D056704:Adaptive Immunity D000369:Aged, 80 and over D000544:Alzheimer Disease D003071:Cognition D000066492:Cognitive Aging D004660:Encephalitis D006801:Humans D017628:Microglia
Alzheimer disease oldest-old immune response microglia T cell gene expression inflammation macrophage