Alzheimer's Alliance, Department of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA.
Division of Epidemiology, Department of Health Sciences Research, Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Alzheimers Dement. 2021 Dec;17(12):2030-2042. doi: 10.1002/alz.12342. Epub 2021 May 13.
Considerable evidence has accumulated implicating a role for immune mechanisms in moderating the pathology in Alzheimer's disease dementia. However, the appropriate therapeutic target, the appropriate direction of manipulation, and the stage of disease at which to begin treatment remain unanswered questions. Part of the challenge derives from the absence of any selective pressure to develop a coordinated beneficial immune response to severe neural injury in adults. Thus, immune responses to the prevailing stimuli are likely to contain both beneficial and detrimental components. Knowledge gaps include: (1) how a biomarker change relates to the underlying biology, (2) the degree to which pathological stage group differences reflect a response to pathology versus trait differences among individuals regulating risk of developing pathology, (3) the degree to which biomarker levels are predictive of subsequent changes in pathology and/or cognition, and (4) experimental manipulations in model systems to determine whether differences in immune biomarkers are causally related to pathology.
大量证据表明，免疫机制在调节阿尔茨海默病痴呆症的病理方面起着重要作用。然而，适当的治疗靶点、适当的操作方向以及开始治疗的疾病阶段仍然是没有答案的问题。部分挑战源自于成年人严重神经损伤时，没有任何选择压力来产生协调的有益免疫反应。因此，对流行刺激的免疫反应可能包含有益和有害的成分。知识空白包括：（1）生物标志物的变化如何与潜在生物学相关，（2）病理阶段分组差异在多大程度上反映了对病理的反应，而个体之间调节发生病理的风险的特征差异，（3）生物标志物水平在多大程度上预测随后的病理和/或认知变化，以及（4）在模型系统中的实验操作，以确定免疫生物标志物的差异是否与病理有因果关系。
