The Role of Chronic Infection in Alzheimer's Disease: Instigators, Co-conspirators, or Bystanders?

IF 3.1 Q2 MICROBIOLOGY Current Clinical Microbiology Reports Pub Date : 2021-12-01 Epub Date: 2021-04-24 DOI:10.1007/s40588-021-00168-6
Lauren Butler, Keenan A Walker
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Abstract

Purpose of review: Herein, we provide a critical review of the clinical and translational research examining the relationship between viral and bacterial pathogens and Alzheimer's disease. In addition, we provide an overview of the biological pathways through which chronic infection may contribute to Alzheimer's disease.

Recent findings: Dementia due to Alzheimer's disease is a leading cause of disability among older adults in developed countries, yet knowledge of the causative factors that promote Alzheimer's disease pathogenesis remains incomplete. Over the past several decades, numerous studies have demonstrated an association of chronic viral and bacterial infection with Alzheimer's disease. Implicated infectious agents include numerous herpesviruses (HSV-1, HHV-6, HHV-7) and various gastric, enteric, and oral bacterial species, as well as Chlamydia pneumonia and multiple spirochetes.

Summary: Evidence supports the association between multiple pathogens and Alzheimer's disease risk. Whether these pathogens play a causal role in Alzheimer's pathophysiology remains an open question. We propose that the host immune response to active or latent infection in the periphery or in the brain triggers or accelerates the Alzheimer's disease processes, including the accumulation of amyloid-ß and pathogenic tau, and neuroinflammation. While recent research suggests that such theories are plausible, additional longitudinal studies linking microorganisms to Aß and phospho-tau development, neuroinflammation, and clinically defined Alzheimer's dementia are needed.

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慢性感染在阿尔茨海默病中的作用:煽动者、共谋者还是旁观者?
综述的目的:在此,我们对研究病毒和细菌病原体与阿尔茨海默病之间关系的临床和转化研究进行了重要综述。此外,我们还概述了慢性感染可能导致阿尔茨海默病的生物学途径:阿尔茨海默病导致的痴呆是发达国家老年人致残的主要原因,但人们对促进阿尔茨海默病发病机制的致病因素的了解仍不全面。在过去的几十年中,大量研究表明慢性病毒和细菌感染与阿尔茨海默病有关。涉及的感染病原体包括多种疱疹病毒(HSV-1、HHV-6、HHV-7)和多种胃肠道和口腔细菌,以及肺炎衣原体和多种螺旋体。这些病原体是否在阿尔茨海默病的病理生理学中起着因果作用仍是一个未决问题。我们提出,宿主对外周或大脑中活跃或潜伏感染的免疫反应触发或加速了阿尔茨海默病的发病过程,包括淀粉样蛋白-ß和致病性 tau 的积累以及神经炎症。虽然最近的研究表明这种理论是可信的,但还需要进行更多的纵向研究,将微生物与 Aß 和磷酸化 tau 的发展、神经炎症和临床定义的阿尔茨海默氏症痴呆症联系起来。
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来源期刊
CiteScore
7.50
自引率
1.90%
发文量
9
期刊介绍: Current Clinical Microbiology Reports commissions expert reviews from leading scientists at the forefront of research in microbiology. The journal covers this broad field by dividing it into four key main areas of study: virology, bacteriology, parasitology, and mycology. Within each of the four sections, experts from around the world address important aspects of clinical microbiology such as immunology, diagnostics, therapeutics, antibiotics and antibiotic resistance, and vaccines. Some of the world’s foremost authorities in the field of microbiology serve as section editors and editorial board members. Section editors select topics for which leading researchers are invited to contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, which are highlighted in annotated reference lists. These timely reviews of the literature examine the latest scientific discoveries and controversies as they emerge and are indispensable to both researchers and clinicians. The editorial board, composed of more than 20 internationally diverse members, reviews the annual table of contents, ensures that topics address all aspects of emerging research, and where applicable suggests topics of critical importance to various countries/regions.
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