Alzheimer's Gone Viral: Could Herpes Simplex Virus Type-1 Be Stealing Your Memories?

Abstract

Alzheimer's disease (AD) is one of the principal causes of disability and morbidity. It is one of the most expensive illnesses. Despite this, there are no significant data regarding its etiology and optimal treatment. This review concentrates on the viral hypothesis of AD. After a comprehensive PubMed literature search, we analyzed the studies associating herpes simplex virus type-1 (HSV1) infection to AD from the previous 10 years. Molecular mechanisms whereby HSV1 induces AD-related pathophysiology, including neuronal production and accumulation of amyloid-beta (amyloid-β), abnormal phosphorylation of tau proteins, impaired calcium homeostasis, and autophagy, are addressed. The virus also imitates the disease in other ways, showing increased neuroinflammation, oxidative stress, synaptic dysfunction, and neuronal apoptosis. Serological studies correlate HSV1 infection with AD and cognitive impairment. A causal link between HSV1 and AD raises the concept of a simple, efficient, and preventive treatment alternative. Anti-viral agents impede brain degeneration by preventing HSV1 spread and its replication, decreasing hyperphosphorylated tau and amyloid-β; thus providing an efficacious treatment for AD. We also mention brown algae, intravenous immunoglobulin (IVIG), and a synthetic drug, BAY57-1293, with anti-viral properties, as options for treating AD. We want to recommend future researchers to look for more affordable, noninvasive, and swifter techniques to identify HSV1 in the brain and assist in the early detection and prevention of AD.

SARS-CoV-2 amyloid, is COVID-19-exacerbated dementia an amyloid disorder in the making?

“…The long-term persistence of symptoms beyond SARS-CoV-2 infection remains to be determined (Gordon et al, 2022 ; Serrano-Castro et al, 2022 ) and a post-pandemic change in dementia rates will take time to show. If COVID-19 is like other viral-induced dementias (Ezzat et al, 2019 ; Khokale et al, 2020 ; Leger et al, 2020 ; Niklasson et al, 2020 ; Saumya et al, 2021 ) and causes exacerbations of AD dementia (Liu et al, 2023 ; Olivera et al, 2023 ) it would be expected that an increase in AD levels post-pandemic may develop over time. The COVID-19 exacerbations of AD dementia (Liu et al, 2023 ; Olivera et al, 2023 ) may increase AD levels post-pandemic over time.…”

“…Intracellular amyloid deposition is thought to trigger neurodegeneration and extracellular plaque formation (Oddo et al, 2006 ). The Aß peptide is neuroprotective, antiviral plus antibacterial (Pearson and Peers, 2006 ; Bourgade et al, 2016 ; Huang, 2023 ) and Aß may be activated in infectious disease states as a protective measure which may explain the suggested viral involvement in Aß aggregation plus AD (Ezzat et al, 2019 ; Khokale et al, 2020 ; Niklasson et al, 2020 ; Liu et al, 2023 ).…”

New Insights into the Molecular Interplay between Human Herpesviruses and Alzheimer’s Disease—A Narrative Review

“…In 1997, Itzhaki and colleagues first provided strong evidence for a linkage between HSV 1 infection and AD, supporting that the reactivation of HSV 1 in the central nervous system is more harmful in AD patients who carry the APOE-ε4 allele and that the combination of these two factors increases the likelihood of disease [ 21 ]. APOE-ε4 allele has been reported to promote brain infiltration by HSV 1, to enhance the attachment and the entry of HSV 1 into the host cells, as well as to increase the viral load in the brain [ 22 , 23 ]. The latter appears to have a detrimental effect on Aβ accumulation, further influencing the Aβ fibril formation and oligomeric Aβ stabilization that is essential for accelerating the early seeding of Aβ pathology [ 22 , 24 ].…”

“…APOE-ε4 allele has been reported to promote brain infiltration by HSV 1, to enhance the attachment and the entry of HSV 1 into the host cells, as well as to increase the viral load in the brain [ 22 , 23 ]. The latter appears to have a detrimental effect on Aβ accumulation, further influencing the Aβ fibril formation and oligomeric Aβ stabilization that is essential for accelerating the early seeding of Aβ pathology [ 22 , 24 ]. It is also noteworthy that APOE facilitates lipid antigen presentation by CD1+ antigen presenting cells to naïve natural killer T (NKT) cells [ 25 , 26 ].…”