Herpes at the root of Alzheimer's?

02 December 2007

Interview with

Professor Ruth Itzhaki, Manchester University

Now sadly, dementia's a disease which is found in increasing numbers of people these days.  It shows itself in lots of different forms from what's called mild cognitive impairment, which affects memory and language, to more ruthless things such as full-blown Alzheimer's disease which can affect daily lifestyle very severely.

Scientists have been looking into Alzheimer's disease for decades and trying to figure out just how it happens.  There's one group based at the University of Manchester that have uncovered one aspect of it that could lead to its prevention.  We sent Meera to find out more.

Meera - Alzheimer's is a form of senile dementia and it's very common.  In fact, one person in five over the age of 80 develops the condition which causes memory loss, sleep disturbance and personality changes.  Patients with the disease show accumulations in their brain with an abnormal protein called beta-amyloid and this is thought to be toxic to the nerve cells: triggering the disease.

Cold sores - a result of Herpes infectionScientists still don't understand exactly what causes the build up of this pathological protein in the first place.  In recent years they've shown that the disease does have a genetic basis but they also suspect there might be another player involved and that's the herpes simplex virus or HSV.  Surprising as it sounds 80% of us are infected with this virus which usually causes cold sores.  What's unusual about HSV is that once you're infected the virus remains in your body for life.  It hides inside nerve cells as a tiny piece of DNA which can periodically reawaken to control the production of new virus particles that then leave the nerve to produce infectious cold sores.  Occasionally the virus can also invade the brain, causing a condition known as encephalitis.  Professor Ruth Itzhaki from Manchester University thinks this might provide us with the clue to how Herpes Simplex is linked to Alzheimer's.

Ruth - The main reason was because in the very serious, rare luckily, illness called herpes simplex encephalitis the virus destroys the same regions as those that are mainly affected in Alzheimer's disease.  Another point is that once people get infected it stays in the body throughout life so it's in a position, possibly, to do harm in old age.

Meera - When it comes to herpes simplex virus, how does it get into our body?  How does it infect our body and how does it work?

Ruth - The main route it takes is transmitted in saliva and probably kissing and so on.  Infants are kissed often and it probably then enters the body and travels in and eventually ends up in what's called the peripheral nervous system.  This is the part of the nervous system other than the brain and the spinal cord.  It stays there for life.

Meera - Once it's in the body what then causes it to become active?

Ruth - It's thought that it reactivates under conditions of stress or when the immune system is suppressed.  A number of causes make it reactivate but I should say that when it reactivates it doesn't necessarily cause any harm in the people at all.

Meera - When research started being done into this connection what was found to connect them?

Microscopy image of a herpes virus.Ruth - The first bit of evidence was when we looked for the virus to find if it was present in brain, viral DNA.  We found that it certainly is present in a high proportion of elderly people.  That led us to continue with the work.  Having found the virus was present in the brain we used other methods which suggested it had been possibly active in the brain and not active just once but maybe recurrently.  We think it might cause a very mild type of disease like encephalitis.  After that we discovered that it looks as if there's an association between the virus in the brain and a bit of the genetic factor, and it's the two together that we think cause the disease in about 60% of Alzheimer patients.

Meera - What's the genetic factor that you thought to link them?

Ruth - It's the type 4 form, so called 'allele,' of a gene called Apolipoprotein E which codes for a protein which is involved with carrying lipids, fats, in blood - in the brain.

Meera - How is this gene thought to work in order to aid herpes and the formation of Alzheimer's?

Ruth - We think it affects a degree of damage.  It may be that there's an early entry of the virus into the brain but we think the main affect is that it affects the extent of damage there.

Meera - So you found this connection now, what next?

Ruth - We've recently been finding rather - I think a major finding - that looks as if the virus does actually cause the formation, or increased formation of an abnormal protein called beta-amyloid which is the main component of one of the abnormal features of an Alzheimer's diseased brain.  We found the virus infection increases that in cells in culture in a mouse brain.  It also, we found, even more strikingly in the sections of human brain post-mortem that it's located within these structures. We think this strongly implicates this in the formation.

Meera - In the grand scale of things is this going to lead to some kind of treatment? I've heard things about a possible vaccine. Is that likely?

Ruth - It is possible in the future but at the moment there's no vaccine for this particular virus. It's something that would have to be developed and would involve a very lengthy clinical trial. People would have to wait for many decades to see whether people do or do not develop the disease when they've been vaccinated. What is much more imminent and practical at the moment would be antiviral treatments which is available fairly cheap and could be used with rather minimal side-effects. It would be good because that the moment there's no real effective treatment against Alzheimer's.

Meera - So Ruth's team have found further evidence connecting herpes simplex virus to the onset of Alzheimer's disease but as she mentioned, there are still many other connections to be found. Teams of scientists across the globe are working in this field, hoping to find a treatment or preventative measure as such a large percentage of our population are affected by this form of dementia.

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