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Cold sores and Alzheimer's

Monday 8 December 2008

The Daily Mail reported that the cold sore virus “may be one of the main causes of Alzheimer’s disease”. The newspaper said researchers have found that the herpes simplex virus 1 (HSV1) could be present in up to 60% of Alzheimer’s cases. There is a suggestion that existing cold sore drugs could be used to treat the condition.

The news coverage could be interpreted to mean the research found that people with cold sores will develop Alzheimer’s or that infection with the cold sore virus alone could cause Alzheimer’s. However, this study was not set up to investigate these questions. It found an association between HSV1 in the brain and brain plaques in Alzheimer’s brains and normal elderly brains. It also found more viral DNA in the plaques from Alzheimer’s brains than plaques from normal brains.

As the researchers state, “association does not prove causality”. They have previously suggested that the virus would most likely work in combination with genetic factors to be causal for Alzheimer’s disease. Larger studies would be needed to better establish this association and to find practical applications to prevent Alzheimer’s. At present, the evidence does not support immunisation or taking antiviral treatments in the hope of preventing Alzheimer’s disease.

Where did the story come from?

This research was conducted by Doctors Wozniak, Mee and Itzhaki and supported by a grant from the Alzheimer’s Society and from the Henry Smith Charity. It was published in the peer-reviewed Journal of Pathology.

What kind of scientific study was this?

In this study the researchers explored a possible link between infection with herpes simplex 1 (HSV1) and Alzheimer’s disease. It was a pathology study in the laboratory using brain samples from dead bodies.  While there are several biological reasons why the two may be linked, these were not explored in this study. The researchers mention previous laboratory studies that assessed the combination of HSV1 in the brain and a specific genetic factor as a risk for Alzheimer’s disease.
The theory underpinning the study was that there could be a link between HSV 1 and Alzheimer’s. This is because HSV1 is associated with a rare brain disorder called herpes simplex encephalitis. This condition affects the parts of the brain that are also most affected by Alzheimer’s disease.

The researchers obtained brain samples from six deceased people with Alzheimer’s and five deceased elderly normal subjects from the South West Dementia Brain Bank in Bristol.They used a technique known as in situ PCR to detect whether there was any evidence of HSV1 DNA in the brain samples. PCR (polymerase chain reaction) as a method is a technique used to replicate DNA molecules from cells in large quantities so that they can be investigated more easily. In situ PCR is an application of PCR techniques that amplifies the genetic material within cells – rather than extracting it first.
In situ PCR increases the number of copies so that DNA can be visualised within the tissue, allowing researchers to precisely visualise and locate a specific type of DNA within tissue.The researchers were interested in whether there was a link (in terms of proximity) between HSV1 and brain plaques in their samples. Brain plaques are clumps of protein deposits found in the brains of people with Alzheimer’s and are a characteristic of the disease. The plaques are also present in the brains of elderly people without Alzheimer’s, but are found in smaller numbers.

What were the results of the study?

The researchers detected HSV1 DNA in all six samples from Alzheimer’s sufferers and in the five elderly normal people. As expected, brain plaques were found in both Alzheimer’s patients and in the brains of normal people.
HSV1 was present in 90% of the brain plaques found in Alzheimer’s patients, and 80% of the brain plaques found in normal patients. The researchers say that these findings, “suggest that the virus might be a cause of plaque formation in many of these subjects”.
The researchers also found that 72% of the viral DNA in the brains of Alzheimer’s disease patients was in plaques, but in normal people only 24% of the viral DNA was in plaques. This means that more of the viral DNA was associated with plaques in Alzheimer’s disease compared with normal people.

What interpretations did the researchers draw from these results?

The researchers conclude that while “association does not prove causality”, alternative explanations for the presence of HSV1 in brain plaques are unlikely. They discuss these alternative explanations in some detail.

What does the NHS Knowledge Service make of this study?

In their write up, the researchers use previously published research by other groups to highlight possible differences between people who get Alzheimer’s and those who do not.They suggest  the possibility that people who do not get Alzheimer’s produce less amyloid (a substance that deposits in the brain and is implicated in the formation of brain plaques), or are better at clearing it.

While the results may support the involvement of HSV1 in the formation of plaques in the brain, there is no indication from this study why some people develop Alzheimer’s while others with brain plaques and HSV1 do not. The success of using in situ PCR to investigate latent (or hidden) infections is an important finding, which will no doubt be used in future research examining the link between HSV1 and Alzheimer’s disease.

This is a small laboratory study that offers preliminary results. Larger laboratory studies, and (more importantly) animal and human studies will be needed before it is known whether this avenue of research will result in a practical application for preventing Alzheimer’s.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Cold sore virus could cause Alzheimer's.

The Daily Telegraph, 7 December 2008

Alzheimer's link to cold sore bug.

The Guardian, 7 December 2008

Cold sore virus could be the clue to the cause of 60 per cent of Alzheimer's cases.

Daily Mail, 7 December 2008

Virus clue to cause of Alzheimer’s.

The Times, 7 December 2008

Alzheimer's virus link found.

The Sun, 7 December 2008

Links to the science

MA Wozniak MA, Mee AP, Itzhaki RF.

Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques.

The Journal of Pathology 2008; 217: 131-138