Viruses - a major cause of amyloid deposition in the brain

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.

KEYWORDS:

• Alzheimer’s disease
• amyloid beta peptide
• viruses
• microbes
• antimicrobial hypothesis

Article highlights

• The amyloid beta hypothesis is outdated.

• Viruses have been implicated as a putative cause of Alzheimer’s disease (AD)

• Viruses contribute either directly or indirectly to amyloid beta production and Tau phosphorylation as well as to neuroinflammation which are the putative hallmarks of AD

• Due to their antiviral effects, amyloid beta peptides are useful but during the disease development, when a threshold is crossed, they become detrimental

• Treatment should aim at preventing the neurotropic viruses to become latent in the brain, by early enough vaccination.

• AD is an inadequate name that should be replaced by Chronic Brain Failure (CBF) of neurodegenerative type.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors have received financial support from the Canadian Institutes of Health Research (CIHR) through the Institutes of Aging [No. 106634], the FRQS (Fonds de Recherche du Quebec) Audace program and the research centers of the CIUSSS de l’Estrie-CHUS, which were awarded to EH Frost and T Fulop. The authors also declare support via the Research Chair Louise-André Charron on Alzheimer’s disease awarded to C Ramassamy. JM Witkowski further declares support via a Polish Ministry of Science and Higher Education statutory grant No. [02-0058/07/262]. Additional support comes from Ikerbasque (The Basque Foundation for Science), from GV-AI-HEALTH, the Basque Government through the BERC 2018-2021 program and the Ministry of Science and Innovation, BCAM Severo Ochoa accreditation CEX2021-001142-S/MICIN/AEI/10.13039/501100011033. Finally, the authors declare support through project RTI2018-093860-B-C21 funded by the European Research Funds co-financed by the Agencia Estatal de Investigación (AEI/FEDER, UE) with the acronym “MathNEURO” and the National Institute for Research in Digital Science and Technology (Inria) via the associated team “[NeuroTransSF]” via M Desroches and S Rodrigues.