阿尔茨海默病是免疫防御动员失败所致吗？来自认知健康的高龄老人的启示。
Is Alzheimer disease a failure of mobilizing immune defense? Lessons from cognitively fit oldest-old.
作者信息
Katsel Pavel, Haroutunian Vahram
机构信息
Department of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Neuroscience, The Icahn School of Medicine at Mount Sinai, New York, NY, USA; Mental Illness Research, Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx, NY, USA.
出版信息
Dialogues Clin Neurosci. 2019 Mar;21(1):7-19. doi: 10.31887/DCNS.2019.21.1/vharoutunian.
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?
多方面的证据支持这样一种假说，即炎症免疫机制促成了阿尔茨海默病（AD）的神经病理学，并且几个免疫特异性基因（TREM2、CR1和CD33）的遗传关联表明，适应不良的免疫反应可能是AD发病机制的关键驱动因素。我们回顾了来自AD尸检研究的与小胶质细胞相关的数据，并检查了来自AD动物模型的支持证据，以回答以下问题：i）AD进展过程中免疫激活的时间顺序是什么，以及它对认知有何影响？ii）在AD与成功的认知衰老中，是否存在不一致的、“预激”的小胶质细胞反应？iii）衰老过程中的中枢神经系统（CNS）修复是否依赖于效应T细胞等细胞适应性免疫反应元件的募集，并且全身免疫细胞的募集能否改善AD神经病理学？iv）目前用于治疗AD的基于免疫系统的治疗方法效果如何？
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