Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer's Disease.
Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer's Disease.
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DOI：
10.2147/ndt.s264910
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发表时间：
2021
影响因子：
3.2
通讯作者：
Witkowski JM
中科院分区：
文献类型：
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作者：
Fulop T;Tripathi S;Rodrigues S;Desroches M;Bunt T;Eiser A;Bernier F;Beauregard PB;Barron AE;Khalil A;Plotka A;Hirokawa K;Larbi A;Bocti C;Laurent B;Frost EH;Witkowski JM
阿尔茨海默病（AD）是痴呆症的最常见形式，并且衰老是发展该疾病的最常见危险因素。AD的病因尚不清楚，但AD可能被认为是一种临床综合征，有多种致病途径。淀粉样蛋白级联假说，声称淀粉样蛋白β（Aβ）的过量产生或清除减少及其聚集成淀粉样蛋白斑块，长期以来被认为是AD的主要原因。然而，许多研究表明，Aβ是数十年来大脑中发生的许多挑战/病理过程的常见结果。实验数据支持的一个关键因素是，导致具有抗菌活性的Aβ产生和沉积的低度感染先于临床上明显的AD的发展。这种感染是慢性的，低度的，由于大脑中几乎有效的抗菌免疫反应，几十年来在临床上基本上是沉默的。诱导慢性炎症状态，导致神经变性。似乎可以预防、延缓或减轻AD发展的干预措施似乎也可以改变这种疾病。在这篇综述中，我们进一步概念化，在衰老过程中，特别是在AD患者的大脑抗菌免疫反应的变化作为一个基础，可能会导致改善治疗策略，预防或减少疾病修饰治疗AD的进展。
Alzheimer’s disease (AD) is the most common form of dementia and aging is the most common risk factor for developing the disease. The etiology of AD is not known but AD may be considered as a clinical syndrome with multiple causal pathways contributing to it. The amyloid cascade hypothesis, claiming that excess production or reduced clearance of amyloid-beta (Aβ) and its aggregation into amyloid plaques, was accepted for a long time as the main cause of AD. However, many studies showed that Aβ is a frequent consequence of many challenges/pathologic processes occurring in the brain for decades. A key factor, sustained by experimental data, is that low-grade infection leading to production and deposition of Aβ, which has antimicrobial activity, precedes the development of clinically apparent AD. This infection is chronic, low grade, largely clinically silent for decades because of a nearly efficient antimicrobial immune response in the brain. A chronic inflammatory state is induced that results in neurodegeneration. Interventions that appear to prevent, retard or mitigate the development of AD also appear to modify the disease. In this review, we conceptualize further that the changes in the brain antimicrobial immune response during aging and especially in AD sufferers serve as a foundation that could lead to improved treatment strategies for preventing or decreasing the progression of AD in a disease-modifying treatment.