Targeting Infectious Agents as a Therapeutic Strategy in Alzheimer's Disease.
Targeting Infectious Agents as a Therapeutic Strategy in Alzheimer's Disease.
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DOI：
10.1007/s40263-020-00737-1
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发表时间：
2020-07
期刊：
影响因子：
6
通讯作者：
Frost, Eric
中科院分区：
文献类型：
--
作者：
Fulop, Tamas;Munawara, Usma;Larbi, Anis;Desroches, Mathieu;Rodrigues, Serafim;Catanzaro, Michele;Guidolin, Andrea;Khalil, Abdelouahed;Bernier, Francois;Barron, Annelise E.;Hirokawa, Katsuiku;Beauregard, Pascale B.;Dumoulin, David;Bellenger, Jean-Philippe;Witkowski, Jacek M.;Frost, Eric
阿尔茨海默病（Alzheimer's disease，AD）是世界上最常见的痴呆症。其原因目前尚不清楚。目前，对AD最常见的解释是淀粉样蛋白级联假说，该假说指出AD的原因是淀粉样蛋白β肽形成老年斑，以及过度磷酸化的tau蛋白形成神经元缠结。第二个新兴的解释AD的理论是基于感染假说。许多实验和流行病学数据支持感染参与痴呆症的发展。根据这一机制，直接或通过微生物毒力因子的感染先于淀粉样蛋白β斑块的形成。具有抗微生物特性的淀粉样β肽在AD的早期阶段可能是有益的，但随着疾病的进展变得有害，伴随着外周和中枢水平的先天免疫系统的改变。感染导致神经炎症，导致全身性炎症并持续全身性炎症，最终导致神经变性和免疫细胞衰老。AD相关微生物的来源是来自肠道、口腔、鼻子和皮肤的各种身体微生物群落。AD的感染假说开辟了新的治疗方法的前景，无论是通过治疗感染本身或调节免疫系统，其衰老，或身体的代谢，无论是单独的，并行的，或以多步骤的方式。
Alzheimer’s disease (AD) is the most prevalent dementia in the world. Its cause(s) are presently largely unknown. The most common explanation for AD, now, is the amyloid cascade hypothesis, which states that the cause of AD is senile plaque formation by the amyloid β peptide, and the formation of neurofibrillary tangles by hyperphosphorylated tau. A second, burgeoning theory by which to explain AD is based on the infection hypothesis. Much experimental and epidemiological data support the involvement of infections in the development of dementia. According to this mechanism, the infection either directly or via microbial virulence factors precedes the formation of amyloid β plaques. The amyloid β peptide, possessing antimicrobial properties, may be beneficial at an early stage of AD, but becomes detrimental with the progression of the disease, concomitantly with alterations to the innate immune system at both the peripheral and central levels. Infection results in neuroinflammation, leading to, and sustained by, systemic inflammation, causing eventual neurodegeneration, and the senescence of the immune cells. The sources of AD-involved microbes are various body microbiome communities from the gut, mouth, nose, and skin. The infection hypothesis of AD opens a vista to new therapeutic approaches, either by treating the infection itself or modulating the immune system, its senescence, or the body’s metabolism, either separately, in parallel, or in a multi-step way.
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