Investigating the Role of Herpes Simplex Virus in Alzheimer's Disease

This report delves into the relationship between Herpes Simplex Virus (HSV) and Alzheimer's disease. It explores the prevalence of HSV, its potential impact on the central nervous system, and its possible link to the development of Alzheimer's. The report discusses research findings, including the detection of HSV in Alzheimer's patients' brains and the role of the APOE-e4 allele. It examines the pathogenesis of Alzheimer's disease, focusing on the amyloid-β precursor protein (APP) and its interaction with HSV. The report highlights how HSV infection affects APP processing, distribution, and transport, potentially leading to cellular damage and the formation of neurofibrillary tangles. Furthermore, it suggests that antiviral strategies may be effective in slowing or preventing the progression of Alzheimer's disease, emphasizing the need for clinical trials to evaluate the efficacy of antiviral medications.

Herpes Simplex Virus as an Outcome of Alzheimer’s disease
Simplex Virus of Herpes is extremely predominant in the population. It occurs almost higher
than 70 percent in the age group of above 50 years. This is a virus which persists in the
peripheral system of nerves latently and it reactivates periodically with the production along with
the viruses which are active. Herpes Simplex Encephalopathy is an acute infection that is
associated with the central nervous system and is a rare disease. Although it is different from h
Disease of Alzheimer, it may lead to bilateral hippocampal that is an internal chronological
lesions which result in thoughtful vocal memory damage which is also a characteristic of
Alzheimer’s disease. Based on the temporal tropism and hippocampal virus and infection, HSV
was considered as a risk factor of environment for Alzheimer’s disease. A research has
concluded that there has been detection of HSV in the Alzheimer’s disease patient’s brain
because of recognition of intrathecal antibodies and DNA virus because of chain reaction caused
by polymerase. However, the brain of normal aged persons also experience the virus in their
brains, it cannot be certified that the infection of HSV is the sole reason of this disease, but its
participation can be observed in the process of pathogens. The frequency of positive subjects of
HSV DNA was not dissimilar between the subjects of control and AD and also the antibodies of
intrathecal were recognized in the same proportions of Alzheimer diseased patients and the
ageing controls shows that the chronic infection of HSV independently is not associated with the
disease of Alzheimer. It is proposed that risk associated with the development of Alzheimer’s
disease which are positive for the DNA HSV present in the normal brain who possessed
apolipoprotein E e4 allele (APOE-e4) portrayed more severity than the individuals who
possessed either single or none of these characteristics. However, these studies remain in the
controversy as it is not confirmed by any other study.

The disease of Alzheimer is a gradual disease related to neurodegeneration which leads to
neurons damage that is irreversible and the damage of abilities of intellects which includes
cognition and memory. As per the characteristics defined by pathology by the tangles caused by
intracellular neurofibrillary and plaques of extracellular senile. While the Alzheimer Disease’s
pathogenesis is still indefinable, it is recognized widely that amyloid-β precursor protein (APP)
plays a significant part in Alzheimer disease’s pathogens which is based on following proof:
beta-amyloid peptide (which is a significant ingredient of plaques of senile which may lead to
death of cells, memory impairment and synaptic defects) is the successor of) amyloid-β precursor
protein. Secondly, if the axonal transport mediated by APP gets disrupted, it leads to
degeneration of neurons which is associated with Alzheimer’s disease. Abnormal APP
phosphorylation may cause production of Abeta, degeneration and stress of cell.
The simplex virus of Herpes is a double stranded neurotropic DNA virus which is inclusive of
subtypes of HSV: 1 and HSV: 2. HSV comprises an internal core DNA, an external envelop, the
tegument and a capsid which is fat membrane consisting of glycoproteins. Almost 60-880 % of
individuals gets infected from the HSV: 1 globally and results in harmful corneal blindness,
deadly encephalitis and general cold sore. HSV is the leading and significant pathogen virus
which is highly infectious and is found in the immunocompromised masses like transplant
receivers. Initially, HSV damages the epithelial cells and tissues and later enters in to the
terminals of sensory nerves. HSV tends to damage the tissues which includes infiltration of cells,
inflammation of perivascular structures and formation of syncytial. During the life cycle of HSV
in sensory system of nerves, HSV moves by the retrograde mode to the neurons bod of cells in
the trigeminal cysts and gradually enters the latency or it replicates. Reactivated and replicated

HSV moves by the anterograde mode out of the body of cells towards the system of central
nerves in addition to membrane of peripheral mucosal.
The studies by RT-PCR have revealed that the presence of DNA of HSV: 1 in the plaques of
temporal and frontal cortices in the post analysis brain of familial and sporadic disease of
Alzheimer. The existence of HSV: 1 in brain is known to be a factor of risk for Alzheimer’s
disease in the aged people who possess the apolipoprotein E ε4 allele. The HSV: 1 viral proteins
in the brain interact with various susceptibility proteins or genes of Alzheimer’s disease.
Additionally, the study of epidemiology portrays that reactivation of HSV: 1 is an intense factor
of risk for Alzheimer’s disease and also the anti-HSV IgG antibody avidity is more in patients
with Alzheimer’s disease and higher in the subjects of impairment of amnestic mild cognition
(which is an early stage of Alzheimer’s disease) instead of control which suggests that the
seropositive IgG would have been accepted as a marker for prodromal diagnosis of mild
cognitive damage of amnesties as well as Alzheimer’s Disease. These information suggest a
relationship between AD pathogenesis and infections caused by HSV. There are many studies
which are focused on the decryption of the mechanisms which are behind this relationship. Many
evidences have shown that infection caused by HSV: 1 have affected the processing of APP
proteolytic, distribution, phosphorylation and transport. A virus related envelop consisting
glycoprotein B consists of a sequence of homologous towards the carboxyl and terminal region
of the Abeta which is APP’s cleavage product. Glycoprotein B’s derivation known as Peptide
accelerates the creation of fibrils of Abeta which are harmful to the primary neurons of cortical.
Acute infection of HSV: 1 affects the proteolytic processing of APP in both the Vivo and Vitro.
APP is isolated with the particles of HSV from the Vero cells infected by HSV: 1 and the
isolated APP particles of HSV are also capable to move the squid axon at the time of injecting it

into the squid action, which suggests that an APP role is significant while mediating the transport
of virus. Subsequent experiments and results in lab have concluded that there was a co-
localization relating to the particles of HSV: 1 with the internal cells of APP under the electron
and epi fluorescent microscopes. A lapse of time live confocal image which has revealed that the
particles of HSV: 1 move together with the internal living cells of APP. The changing interaction
and relationship between the APP and HSV: 1 results in the consequences and outcomes of
pathology. The infection of HSV: 1 lowers the velocity of vesicles of APP on an average which
causes the mal distribution of APP in the cells which are infected.
APP’s Mis-localization and Compromised transport may lead to higher proteolysis of APP with
infection of HSV: 1 infection, which may lead to injury of cells. Additionally, infection of HSV:
1 in the cell lines of human neurons enhances the tau proteins’ phosphorylation which is the
significant component of tangles of neurofibrillary, which is considered as the AD’s hallmark.
UL13, which is a virus related kinase which will phosphorylate the tau proteins of humans.
Additionally, the cells which are infected with HSV: 1 gets treated with acyclovir which is the
significant agent of antivirus use to treat the HSV: 1 infection after targeting the replication of
DNA virus reduces substantially the phosphorylated tau protein and Abeta Amount which are the
two perpetrators of AD. This outcome gives support to the concept of involvement of HSV
infection in the pathogenesis of Alzheimer’s disease and also opens the window to stop or slow
the process of Alzheimer’s disease with strategies of antiviruses.

Conclusion
Aggregately, all epithelial cells and range of neurons gets infected by HSV: 1 and moves the
epithelial cells and neurons in two directions. The functions of HSV include active usurping of
functional machinery which is intact to various cellular machinery of biology by having an
interaction with the cell based proteins for the egress, DNA replication, transcription and entry.
The repeated reactivation and infection of HSV leads to hyper tau proteins of phosphorylation
and biogenesis disturbance, localization of subcellular, proteolytic and phosphorylation
processing of the APP. The existing infection of the HSV all among the individuals globally, the
relationship of intense infection of HSV to Alzheimer’s disease and the possible usage of HSV
for the therapy of gene as a transferring vector, it is authoritative to relate the interactive
mechanism between cellular proteins and HSV that are linked with Alzheimer’s Disease. The
Clinical trials to evaluate the efficiency of antiviral medicines and drugs while treating
Alzheimer’s disease are needed in urgent basis.