Scientists have exposed a connection between human herpes virus and Alzheimer’s, show how viral transposable elements accelerate the brain’s brain. The good news? Antiviral medicines such as ValacyClovir can delay or even prevent the disease.
Study: Human herpes virus-associated transposable element activation in human aging brain with Alzheimer’s disease. Image Credit: Design_Cells / Shutterstock.com
A recent study published in Alzheimer and dementia Investigates how human herpes virus (HHV) contributes to the pathophysiology of Alzheimer’s disease (AD).
How does herpesinfection influence the risk of advertising?
More than 30 years ago, researchers discovered a greater prevalence of the human Simplex virus type 1 (HSV-1) DNA in the brains of people who died of AD compared to healthy individuals. In this population, the incidence of AD more often took place in that with a history of HSV-1 infection rates, with Apolipoprotein 4 (Apoe4) Carriers with recurring HSV-1 reactivation speeds also with a greater risk of developing AD.
Last in vitro And In Vivo Rodent studies have reported that mice that are infected with HSV-1 develop both neuro inflammation and protein abnormalities, including amyloid-beta and tau changes that are characteristic of AD. In the current study, the researchers investigated the potential role of HHV infection-associated transposable elements (TE’s) in ad-specific neurodegeneration.
What are transposable elements?
Te’s are mobile genetic elements (MGEs) or small pieces of genetic material that can be activated and then moving through the genome. As Te’s merge with DNA at their new location, they can cause significant interruptions in nearby genes, which means that the way these genes function change.
Aging is associated with increasing te -activation. Previously, changes in te -activation were involved in various cognitive disorders.
About the study
Data on gene function was obtained from the functional Genomics databases of the religious orders study of the Rush Memory and Aging Project (ROS/MAP) and Mount Sinai Brain Bank (MSBB) Brain biobanks. Transcripts with one cells were investigated from the fortresses of deceased persons with and without advanced AD to identify changes on a molecular level in the HHV-positive AD brain significance for neurofibrillary Tangle (NFT) formation.
In -activation changes were assessed by Celsubset. The association of activated ins with amyloid beta (Aβ) and Tau -Pathology was also investigated. HHV-positive pre-brain were investigated to validate the observations.
Study findings
HHV -Ribonucleic acid (RNA) was more often identified in the brains of individuals with the Apoe4 genotype. Increased expression of HHV -RNA was also observed in the brains of people with a more advanced AD as assessed by the Braak -enscenering and the consortium to draw up a register for the scores of Alzheimer Disease (Cerad).
Several TEs were extensively activated in the HHV-positive AD brain, but not those of healthy individuals. In addition, changes in ad-tasted brain reflected the presence of neuro inflammation and microglial activation.
The long exhausted nuclear element (Line) class was the most regulated too, in particular the Line1 sub -family te’s. These TEs were activated in astrocytes and microglia in ad-brain, which suggests that their role in stimulating cell survival and proliferation by a G-protein-linked receptor (GPCR).
Line1 TEs have also registered the targets LNCRNA Nuclear Enriched Abundant Transcript 1 (Nearer 1) and inositol trifhospate 3-kinase B (ITPKB). Nearer 1 Is involved in AD progression and neuro inflammation.
All in all, these findings indicate that HHV infection can cause neuro inflammation through the activation of line 1 in astrocytes.
The expression of the ten most differential increased te’s in AD brain was significantly different from the one observed in healthy individuals, which indicates the diagnostic potential of these te’s. Female specific changes were also observed in some Line1 sub-family ins.
In -dys regulation it is possible to correct by antiviral drugs
Anti-HHV medicines, in particular Valacyclovir and AceClovir, partially corrected widespread te-activation in response to HHV to brain organoids infected by HSV-1.
This in vitro Observation was validated by investigating data from 80 million health files in a public database using artificial intelligence to determine the incidence of advertisements after antiviral recipe for HSV-1 infection. This analysis identified a significantly lower incidence of AD in persons who prescribed Valacyclovir and AceClovir, with these improvements more prominent in women than men, as well as individuals aged 75 and older.
What is ValacyClovir?
In vitro Assays indicated that treatment with Valacyclovir did not prevent the formation of Tau clonts. Valacyclovir treatment, however, accelerated their breakdown, preventing their progression to NFTs.
The treatment of ValacyClovir also reduced Tau phosphoryleming and inactivated line Te’s, in addition to reversing the aggregation of Line1-open reading frame 1p (ORF1P) by stimulating autophagia without influencing the protein excess levels.
Anti-HHV drugs can suppress virus replication during reactivation events. By preventing viral proliferation in infected host cells, these medicines can reduce the future risk of AD.
Conclusions
Based therapies can offer potential therapeutic approaches for the prevention and treatment of HHV-Associed AD or other AD-related dementia’s if widely applied. “
Journal Reference:
- Feng, Y., Cao, S., Shi, Y., et Alt Alto. (2025). Human herpes virus-associated transposable element activation in human aging brain with Alzheimer’s disease. Alzheimer and dementia. DOI: 10,1002/Alz.14595.