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病毒——大脑中淀粉样蛋白沉积的主要原因。

Viruses - a major cause of amyloid deposition in the brain.

作者信息

Fulop Tamas, Ramassamy Charles, Lévesque Simon, Frost Eric H, Laurent Benoit, Lacombe Guy, Khalil Abedelouahed, Larbi Anis, Hirokawa Katsuiku, Desroches Mathieu, Rodrigues Serafim, Bourgade Karine, Cohen Alan A, Witkowski Jacek M

机构信息

Research Center on Aging, Centre Intégré Universitaire de Santé Et Services Sociaux de l'Estrie-Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.

Department of Medicine, Division of Geriatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.

出版信息

Expert Rev Neurother. 2023 Jul-Dec;23(9):775-790. doi: 10.1080/14737175.2023.2244162. Epub 2023 Aug 9.

DOI:10.1080/14737175.2023.2244162
PMID:37551672
Abstract

INTRODUCTION

Clinically, Alzheimer's disease (AD) is a syndrome with a spectrum of various cognitive disorders. There is a complete dissociation between the pathology and the clinical presentation. Therefore, we need a disruptive new approach to be able to prevent and treat AD.

AREAS COVERED

In this review, the authors extensively discuss the evidence why the amyloid beta is not the pathological cause of AD which makes therefore the amyloid hypothesis not sustainable anymore. They review the experimental evidence underlying the role of microbes, especially that of viruses, as a trigger/cause for the production of amyloid beta leading to the establishment of a chronic neuroinflammation as the mediator manifesting decades later by AD as a clinical spectrum. In this context, the emergence and consequences of the infection/antimicrobial protection hypothesis are described. The epidemiological and clinical data supporting this hypothesis are also analyzed.

EXPERT OPINION

For decades, we have known that viruses are involved in the pathogenesis of AD. This discovery was ignored and discarded for a long time. Now we should accept this fact, which is not a hypothesis anymore, and stimulate the research community to come up with new ideas, new treatments, and new concepts.

摘要

引言

在临床上,阿尔茨海默病(AD)是一种具有多种认知障碍谱系的综合征。病理学与临床表现之间存在完全脱节的情况。因此,我们需要一种突破性的新方法来预防和治疗AD。

涵盖领域

在本综述中,作者广泛讨论了淀粉样蛋白β并非AD病理原因的证据,这使得淀粉样蛋白假说不再站得住脚。他们回顾了微生物,尤其是病毒,作为触发/导致淀粉样蛋白β产生的原因,并引发慢性神经炎症作为数十年后以AD临床谱系表现出来的介质的作用的实验证据。在此背景下,描述了感染/抗菌保护假说的出现及后果。还分析了支持这一假说的流行病学和临床数据。

专家观点

几十年来,我们已经知道病毒参与了AD的发病机制。这一发现长期以来被忽视和摒弃。现在我们应该接受这一已不再是假说的事实,并激励研究界提出新的思路、新的治疗方法和新的概念。

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