肺炎衣原体和SARS-CoV-2感染与阿尔茨海默病的发病机制。

IF 4.5 2区 医学 Q2 GERIATRICS & GERONTOLOGY
Frontiers in Aging Neuroscience Pub Date : 2025-06-13 eCollection Date: 2025-01-01 DOI:10.3389/fnagi.2025.1587782
Alexa Romanella, Maegan McCall, Rachel Corwin, Alaha Abdul Faruq, Emily Lingo, Sanya Bhambhani, Christine J Hammond, Brian J Balin
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引用次数: 0

摘要

阿尔茨海默病(AD)是世界上最常见的神经退行性疾病,但我们对其因果关系的了解仍然缺乏。目前一项基于证据的假设提出,某些感染因子引发了与阿尔茨海默病一致的神经退行性变。与阿尔茨海默病发病相关的两种感染因子是肺炎衣原体(Cpn),一种呼吸道专性细胞内细菌,以及严重急性呼吸综合征冠状病毒2 (SARS-CoV-2),一种导致COVID-19大流行的冠状病毒。这两种微生物都可能使易感人群易患AD等疾病。方法:本综述主要收集同行评议的原始研究和综述文章,评估Cpn和SARS-CoV-2与AD的潜在关联。我们的研究重点包括:APOEε4和AD常见的其他生物标志物的遗传风险,包括白介素-6 (IL-6)、趋化因子配体2 (CCL2)、neuropilin-1 (NRP1),以及感染过程和由此产生的神经炎症的结构/功能方面。结果:Cpn和SARS-CoV-2均可通过感染嗅觉系统神经上皮进入大脑。Cpn与硫酸肝素蛋白聚糖结合进入粘膜细胞。SARS-CoV-2与ACE2受体结合后感染上皮细胞。一旦进入神经上皮,病原体可能会转移到嗅球。NRP1是AD中丰富的受体,也会增强SARS-CoV-2感染。此外,这两种病原体都可能进入体循环,最终通过血脑屏障进入。SARS-CoV-2刺突蛋白与CCL2一起共同刺激巨噬细胞,导致IL-6细胞因子释放。同样,Cpn感染导致CCL2和IL-6细胞因子释放增加。任何一种生物体的原发性感染都可能导致IL-6水平的长期升高和继发性感染。此外,宿主APOEε4的表达似乎增加了对Cpn和SARS-CoV-2感染的易感性。讨论:Cpn和SARS-CoV-2可能通过嗅觉神经上皮细胞和/或通过血脑屏障进入大脑。SARS-CoV-2利用特异性受体进行感染,而Cpn利用蛋白聚糖的结合。神经炎症可能是一种或两种生物体感染的结果,CCL2和IL-6水平升高导致AD发病。两种表达APOEε4的生物体的感染均存在遗传风险。正在进行的和未来的研究将进一步剖析SARS-CoV-2和Cpn感染的机制,因为它们可能为阿尔茨海默病的病因和诊断因素提供信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Infections with Chlamydia pneumoniae and SARS-CoV-2 and Alzheimer's disease pathogenesis.

Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the world, but our understanding of causation is still lacking. A current evidence-based hypothesis proposes that certain infectious agents initiate the neurodegeneration consistent with AD. Two infectious agents correlated to AD pathogenesis are Chlamydia pneumoniae (Cpn), a respiratory obligate intracellular bacterium, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus responsible for the COVID-19 pandemic. Both organisms may predispose susceptible populations to disease manifestations, such as AD.

Methods: This review focused on peer-reviewed original research and review articles evaluating the potential association of Cpn and SARS-CoV-2 with AD. Our focus included: genetic risk with expression of APOEε4 and other biomarkers common to AD including interleukin-6 (IL-6), chemokine ligand 2 (CCL2), neuropilin-1 (NRP1), and structural/functional aspects of the infectious processes and resultant neuroinflammation.

Results: Both Cpn and SARS-CoV-2 may infect the neuroepithelium of the olfactory system to enter the brain. Cpn binds to heparan sulfate proteoglycans for entry into mucosal cells. SARS-CoV-2 infects epithelia after binding to ACE2 receptors. Once inside the neuroepithelium, the pathogens may traffic to the olfactory bulbs. NRP1, an abundant receptor in AD, also potentiates SARS-CoV-2 infection. Furthermore, both pathogens may enter the systemic circulation for eventual entry through the blood brain barrier. The SARS-CoV-2 spike protein, in conjunction with CCL2, co-stimulates macrophages, resulting in IL-6 cytokine release. Likewise, Cpn infection leads to an increase of CCL2 and IL-6 cytokine release. The primary infection of either organism may lead to chronically elevated levels of IL-6 and secondary infection(s). Additionally, host APOEε4 expression appears to increase susceptibility to Cpn and SARS-CoV-2 infections.

Discussion: Cpn and SARS-CoV-2 may enter the brain through olfactory neuroepithelial cells and/or through the blood brain barrier. SARS-CoV-2 utilizes specific receptors for infection, while Cpn utilizes binding of proteoglycans. Neuroinflammation may be an outcome of infection with one or both organisms as observed by increased levels of CCL2 and IL-6 leading to AD pathogenesis. Genetic risk is noted for infection with both organisms with expression of APOEε4. Ongoing and future studies will further dissect mechanisms of infection with SARS-CoV-2 and Cpn as they may inform on causation and diagnostic factors for AD.

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来源期刊
Frontiers in Aging Neuroscience
Frontiers in Aging Neuroscience GERIATRICS & GERONTOLOGY-NEUROSCIENCES
CiteScore
6.30
自引率
8.30%
发文量
1426
期刊介绍: Frontiers in Aging Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the mechanisms of Central Nervous System aging and age-related neural diseases. Specialty Chief Editor Thomas Wisniewski at the New York University School of Medicine is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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