Viral Infections, Are They a Trigger and Risk Factor of Alzheimer’s Disease?

Meagan D. Rippee-Brooks; Wenzhe Wu; Jianli Dong; Miguel Pappolla; Xiang Fang; Xiaoyong Bao

doi:10.3390/pathogens13030240

Pathogens (Mar 2024)

Viral Infections, Are They a Trigger and Risk Factor of Alzheimer’s Disease?

Meagan D. Rippee-Brooks,
Wenzhe Wu,
Jianli Dong,
Miguel Pappolla,
Xiang Fang,
Xiaoyong Bao

Affiliations

Meagan D. Rippee-Brooks: Microbiology and Immunology Graduate Program, Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77550, USA
Wenzhe Wu: Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 77550, USA
Jianli Dong: Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77550, USA
Miguel Pappolla: Department of Neurology and Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, Galveston, TX 77550, USA
Xiang Fang: Department of Neurology and Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, Galveston, TX 77550, USA
Xiaoyong Bao: Microbiology and Immunology Graduate Program, Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77550, USA

DOI: https://doi.org/10.3390/pathogens13030240
Journal volume & issue: Vol. 13, no. 3
p. 240

Abstract

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Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe cute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD such as the lytic replication and axonal transport of HSV-1, the various mechanisms of ZIKV neurotropism through the human protein Musashi-1 (MSI1), and the spread of SARS-CoV-2 through the transfer of the virus through the BBB endothelial cells to glial cells and then to neurons via transsynaptic transfer. We will also explore beyond these mere associations by carefully analyzing the potential mechanisms by which these viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, the dysregulation of immune responses, and the impact on protein processing (Aβ42 and hyperphosphorylated tau). Controversies and challenges of the virus–AD relationship emerge as we tease out these potential mechanisms. Looking forward, we emphasize future directions, such as distinct questions and proposed experimentations to explore, that the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development while encouraging further discussion.

Published in Pathogens

ISSN: 2076-0817 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine
Website: http://www.mdpi.com/journal/pathogens

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