Herpes & Alzheimers linked

[Dr Mordrid]

IMO this is a general interest thread, not just for the science geeks.

http://www.livescience.com/humanbiology/070103_herpes_alzheimers.html

Herpes Might Cause Alzheimer's

By Robin Lloyd
Senior Editor
posted: 03 January 2007
02:24 pm ET
Updated 3:01 p.m. ET

New research supports growing concerns that herpes plays a role in the development of Alzheimer’s disease, the most common form of dementia.

The latest work, announced today, shows a link between a gene and herpes simplex 1, or HSV. The form of the ApoE gene called ApoE-4 is the leading known risk factor for Alzheimer’s. And HSV is the form of herpes that causes cold sores around the mouth. More than 80 percent of Americans are infected with HSV.

The researchers, at the University of Rochester Medical Center, found that ApoE-4 effectively puts out a welcome mat for the herpes virus, allowing it to be more active in the brain.

“The data suggest that ApoE-4 may support the ability of HSV to be a more virulent pathogen,” said Howard Federoff, lead author of the research published online in the journal Neurobiology of Aging.

The research involved measuring the activity levels of HSV in the brains of mice with different forms of the human ApoE gene.

The team found that the virus infiltrates brain cells about the same whether or not mice have the ApoE-4 form of the gene. But in mice with the ApoE-4 version, the virus is less likely to be latent and thus more likely to multiply.

Scientists have known for several years that the ApoE-4 gene plays a role in Alzheimer’s but the idea that it works in concert with the herpes virus is new.

Ruth Itzhaki of the University of Manchester has conducted several studies showing a correlation between herpes and Alzheimer’s. Patients suffering from the dementia disease who also have the ApoE-4 form of the gene also have more herpes DNA in the brain regions that are affected by Alzheimer’s, she found. And people with the ApoE-4 version of the gene who have HSV are more likely to get Alzheimer’s than those who lack either the gene version and the virus.

Also, other scientists have found that people who frequently break out in cold sores are more likely to have the gene that makes them more vulnerable to Alzheimer’s.

HSV is a chronic infection that lives in people for a lifetime, periodically flaring up. The virus is usually latent, locked inside cells, but occasionally stress, fatigue, certain foods and even sunlight can spark the virus into an active phase that damages cells and causes cold sores.

[Brian Ellis]

Above all, NOT for the science geeks.

[Dr Mordrid]

IMO if shown true Dr. Itzhaki's team could be getting into Nobel territory, especially if they find a way to block the HSV/ApoE-4 association.

Alzheimer's is a horrid disease and anyone who contribute to its demise is worth of every laurel available, and more.

[Brian Ellis]

Alzheimer's is a horrid disease and anyone who contribute to its demise is worth of every laurel available, and more.

Agreed! But my previous remark was because the article presents a possible hypothesis, not a scientific proof!

[cjolley]

Are they saying there is a causal relationship?
The article doesn't seem to make that clear.
All I see is the relationship between two strangers because they take the same subway to work.

Is there more there that I'm not seeing?

[Elie]

If true, I could be amongst those who may get Alzheimers I used to get cold sores every month at least once.
Now that rate has changes to once every 3-4 months, but still.

[Dr Mordrid]

Are they saying there is a causal relationship?
The article doesn't seem to make that clear.
>
Is there more there that I'm not seeing?

The ApoE-4 gene is a known agent in mouse and human Alzheimer's. What has been at question is what external factor triggers the disease. They have pretty much shown that in mice HSV1 is a trigger, and mice are an excellent analog for human disease. The next step is transferring the research to human cells etc.

The combination of a genetic factor plus an infectious trigger is now suspected to cause many, many diseases.

[cjolley]

I still don't see where anything in the article implies a causal relationship except the title.

That Herpes and Alzheimer's are both potentiated by the same gene does not mean that Herpes causes Alzheimer's anymore than it means Alzheimer's causes Herpes.

Maybe they left something out of the article?

The closest I see is "...Patients suffering from the dementia disease who also have the ApoE-4 form of the gene also have more herpes DNA in the brain regions that are affected by Alzheimer’s,..."

Is that because herpes causes the Alzheimer's or because those are the regions where the gene is active?
Maybe Alzheimer's causes brain cells to be more susceptible to herpes virus.

The causal part just seems thin to me.

[Dr Mordrid]

Try this one;

http://www.physorg.com/news87049745.html

>
The work suggests that ApoE-4 may alter the balance between the HSV life cycle forms. It's possible that the ApoE gene works as a sort of bodyguard that tries to keep cells safe from herpes, perhaps by facilitating latency. Somehow the ApoE-2 version is extremely effective at keeping the virus at bay, while in this study, the ApoE-4 version wasn't any more effective than not having an ApoE gene at all.

The ApoE gene is well known to Alzheimer's researchers. The gene, which normally plays a role in ferrying cholesterol around the body, is associated with both the cellular tangles and amyloid plaques that are found in the brains of patients with the disease. Researchers have found several ways in which the gene might make a person vulnerable to getting a disease like Alzheimer's. In people with the ApoE-4 gene, brain cells don't seem to recover as well from injury, and the cells don't form new connections as well as cells equipped with either ApoE-2 or ApoE-3. Other scientists have shown that the gene plays a role in clearing toxic amyloid beta from the brain.

"Just how ApoE-4 makes people vulnerable to Alzheimer's disease isn't resolved at all," said Federoff, who is director of the University's Center for Aging and Developmental Biology. "It may be that it works in multiple ways."

The team is exploring different ways that herpes might affect the development of Alzheimer's disease. In one study the team looking at the role of Nectin-1, a cell adhesion molecule that herpes uses as one route to infect a cell. Nectin-1 plays a crucial role in forming synapses, the structures between brain cells that move information and signals from one cell to the next. The team is studying whether herpes somehow disturbs the receptor, possibly altering the structure and function of the synapse. Damage to synapses is one of the earliest signs of Alzheimer's disease.

Another possibility is that the body's immune response against herpes somehow damages the brain, and that such damage is worse in people with the ApoE-4 copy of the gene. Earlier this year Federoff's team published a study that showed inflammation is the earliest change that could be detected in a brain affected by Alzheimer's disease, before any of the hallmark plaques or tangles and certainly long before any behavioral changes are seen. Such inflammation often is a byproduct when the immune system fights an infection.
>

[cjolley]

Much better.

I like the last paragraph.

[Brian Ellis]

Yes, but it is still "exploring" and "another possibility" etc. In other words, vague hypotheses. I hope that something does come from the research, but it is far too early to be more than hopeful. There are other viruses that are similar to that which causes herpes simplex, such as herpes zoster and chickenpox. In 1970, I had a near-fatal encephalitis caused by the zoster virus (off work for >3 months, permanent sequelae of character change and short-term memory loss). Then, if 80% of the population are infected with h. simplex, what are the statistical probabilities of those infected developing Alzheimer's, compared with the other 20%? Still lots of questions to be answered.