I've been in email contact with Dr Ruth Itzhaki of Manchester University. Her team have found and explored a possible link between HSV-1 and Alzheimer's, a link which other researchers have apparently confirmed. I contacted her because I increasingly feel that S's herpes outbreaks always coincide with a worsening of her symptoms but I have also found that when she takes Aciclovir (anti-viral medication) to shorten the herpes outbreak - and admittedly she has only taken it twice - there are some signs of an increase in lucidity.
Dr Itzhaki tells me that there is no interest in funding this research and that her team may cease to exist in the near future. If you read the summary of the research (below) you may, like me, be flabbergasted.
Role
of a virus in Alzheimer’s disease, and prospects of treatment with
antiviral agents
Almost
18 million people worldwide suffer from Alzheimer’s disease (AD)
and unfortunately, this figure will rise as longevity increases. The
need for effective treatments is therefore extremely urgent. (Current
treatments alleviate symptoms but do not prevent further
deterioration.) Most AD
researchers investigate the disease’s main characteristics –
abnormal structures in brain called tangles and plaques which are
probably important
features of the disease;
however, despite the vast amount of information gathered about the
structures, the causes
of their formation are unknown.
Our
research, which has strongly implicated a common virus in the
development of the disease, is completely original and offers a
direct route to treatment: very effective and safe antiviral agents
are available to combat the virus and thus to treat AD patients. It
indicates also the future possibility of preventing the disease by
vaccination against the virus in infancy.
The
virus implicated in AD, herpes simplex virus type 1 (HSV1), is the
one that causes cold sores.
It infects most humans in infancy and thereafter remains in the body
in latent (i.e., dormant) form within the peripheral nervous system
(the part of the nervous system other than the brain and spinal
cord). From time to time – for example if the person is stressed –
the virus becomes activated and in some people it then causes cold
sores..
We
found that the virus is present also in brain, in many elderly
people, that it confers a strong risk of AD when in the brain of
people who have a specific genetic factor (APOE-e4), and that it does
become activated, perhaps recurrently, in brain. The
likelihood of developing AD is 12 times greater for APOE-e4 carriers
with HSV1 in brain than for those with neither factor.
Subsequently,
we linked HSV1 directly
to AD plaques and tangles. We discovered that the viral DNA is
located very specifically in plaques. We found also that the main
component of plaques, beta amyloid (Aβ), accumulates in
HSV1-infected cell cultures and in the brains of infected mice. Taken
together, these results suggest that HSV1 is a cause of toxic amyloid
products and plaques. We have shown too that the main component of
tangles – hyperphosphorylated tau – accumulates in HSV1-infected
cell cultures. Studies by other groups have confirmed the
HSV1-induced formation of Aβ and abnormal tau. Possibly, infected
cells produce Aβ and abnormal tau as part of their “innate”
immune system, in an attempt to protect against HSV1, but eventually
these molecules are over-produced and then cause damage.
Alternatively, cells may produce them because they are needed by HSV1
for its replication (the virus subverts the cell’s machinery to
produce, in general, only such proteins).
We
propose that HSV1 enters the brain in the elderly as their immune
systems decline, establishes a latent infection from which it
is
repeatedly reactivated by events such as stress, immunosuppression,
and brain inflammation induced by systemic infection, and that
repeated activation causes cumulative damage* and eventually AD, in
APOE-e4 carriers. (Other studies of ours support the concept that
genetic factors can determine the severity of a microbial disease in
showing that in the case of several diverse microbes, APOE affects
outcome of infection. Probably significantly, we found APOE-e4 to be
a risk for cold sores.) The mechanism might involve up-regulation of
enzymes involved in Aβ formation and, via the known inhibitory
effect the virus has on autophagy, prevention of abnormal protein
degradation. Aβ might be produced as part of the cell’s defence
response, initially entombing the agent and thereby preventing
further damage to the host, but eventually, through overproduction,
resulting in toxicity via oligomer formation. Infected cells, after
suffering severe structural damage, die and disintegrate, releasing
amyloid aggregates which develop into plaques after other components
of dying cells are deposited on them. Presumably, in APOE-ε4
carriers, AD develops either as a consequence of greater HSV1-induced
formation of toxic Aβ products, or as a direct consequence of
virus-induced cell death or inflammation.
Our
data suggest that antiviral agents might be used for treating AD.
Currently available antiviral agents act by targeting replication of
HSV1 DNA, and so we considered that they might be successful in
treating AD only if the accumulation of Aβ and P-tau caused by HSV1
occurs at or after the stage at which viral DNA replication occurs.
If these proteins are produced independently of HSV1
replication, antivirals might not be effective. We investigated
this and found that treatment of HSV1-infected cells with acyclovir,
the most commonly used anti-HSV antiviral agent, and also with two
other anti-HSV antivirals, does indeed decrease Aβ and P-tau, as
well as decreasing HSV1 replication (as expected).
We
conclude that anti-HSV antiviral agents would be suitable for
treating AD to reduce disease progression, with the great advantage
that unlike current therapies, only the virus, not the host cell,
would be targeted. Also, other viral damage besides Aβ and P-tau
production that might be involved in AD pathogenesis would be
inhibited. Further, ACV is very safe and relatively inexpensive.
*This
is supported by a study by a prominent US virologist who has recently
found that repeated activation of HSV1 in infected mice over
a long period of time causes the formation of lesions in their brains
