Fw: Can you catch Alzheimer¹s disease? theory links it with herpes virus

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Can you catch Alzheimer's disease?

Controversial theory links the memory-erasing condition to herpes virus

By Tom McGrath

Mens Health

updated 12:20 p.m. ET, Sun., Oct . 25, 2009

Rich P. is only in his 20s, but these days he finds himself obsessing over

something most guys his age never think twice about: Am I doomed to lose my

mind?

In some ways, Rich's anxiety is understandable. " My girlfriend is a social

worker who works with the aged, specifically people with Alzheimer's, " he

says. " So I've seen close up what the disease does to you. " Indeed,

Alzheimer's disease is characterized by memory loss and confusion, and

typically ends with complete disconnection from the world. People in its

advanced stages can't care for themselves, recognize loved ones, or remember

the lives they lived. (Worried about losing your memory and health as you

age? Discover the age erasers for men that can strip away 10 years and leave

you looking and feeling younger, longer!)

There's also another, even more personal connection for Rich: His

girlfriend's father recently passed away from Alzheimer's. He was one of

more than 70,000 Americans who die from the disease every year.

Still, what should worry Rich most isn't what he's witnessed in other

people, but what he sees in the mirror. Because there, literally right under

his nose, is evidence that the monster that could be responsible for

Alzheimer's is already skulking about inside his body, preparing itself-at

some point, decades down the road-to attack and destroy his brain.

So here's the question: Is it in you, too?

For years, physicians and Alzheimer's experts have said that the earliest

symptoms of the disease typically don't appear until you're in your 60s,

70s, or beyond. But now there's reason to believe that the first warning

signs may actually crop up much earlier than that, and in a seemingly much

more benign way: as cold sores, those embarrassing blisters that can erupt

on the lips of people who are sick or run-down.

The sores are triggered by the herpes virus ‹ most often, herpes simplex

virus type 1 (not to be confused with HSV-2, which predominately causes

genital herpes). In recent years, a growing body of research, much of it

championed by a British scientist, has begun to suggest a startling fact:

The same virus known for sabotaging people's social lives could be

responsible for the majority of Alzheimer's cases.

" There's clearly a very strong connection, " says the researcher, Ruth

Itzhaki, Ph.D., speaking one afternoon in her office at the University of

Manchester, in northwestern England. A neurobiologist, Itzhaki has spent the

better part of two decades studying the link between herpes and Alzheimer's.

" I estimate that about 60 percent of Alzheimer's cases could be caused by

the virus. "

As viruses go, herpes is a particularly devilish bugger. The ancient Greeks

were among the first to record the sores it causes (the virus's name is

derived from a Greek word meaning " to creep " ), and today the microbe is

ubiquitous. As many as 85 percent of us have been infected by it, though

experts say as few as 15 percent show symptoms. Worse, once you have it, you

have it forever: After the initial infection, the virus lies dormant in your

peripheral nervous system, occasionally flaring up during periods of stress,

illness, or fatigue. You can follow these three steps to prevent a herpes

outbreak, but it never completely disappears.

And it's that fact ‹ herpes as the viral equivalent of The Thing That

Wouldn't Leave ‹ that lies at the heart of the herpes-Alzheimer' s

relationship. Research suggests that as we age, HSV-1 actually spreads to

our brains, where in certain people, Itzhaki theorizes, it can cause the

buildup of deposits ‹ known as amyloid plaques and neurofibrillary tangles ‹

that attack and destroy the cells responsible for memory, language, and

physical functions. In short, those people develop Alzheimer's.

It's a provocative theory, one that would sound preposterous if it weren't

for the steadily accumulating evidence. Last January, for instance, Itzhaki

and her colleague, Wozniak, Ph.D., published a study in the Journal

of Pathology in which they searched for the presence of the herpes virus in

people's brains. They found that it resided in 90 percent of the amyloid

plaques.

" The link between herpes and Alzheimer's has been there for a while, but

more people are starting to pay attention, " says Federoff, M.D.,

Ph.D., an expert on neurodegenerative diseases and the executive dean of the

school of medicine at town University. " It's no longer just a

curiosity. "

The cold sore connection

Unfortunately, while the theory may be on more researchers' radar, it's

perhaps becoming a blip in the one area that matters most: the fight for

funding. Sure, on the surface, the possible discovery of a cause for

Alzheimer's looks like Nobel-caliber news because it suggests a way forward

in treating a disease that scientists have struggled ‹ largely

unsuccessfully ‹ to understand. What's more, if a new treatment does emerge,

it could be just in the nick of time: Thanks to a combination of changing

demographics and longer life spans, experts are predicting nothing less than

an Alzheimer's epidemic in the decades ahead.

And yet all the promise held in the herpes connection may vanish as quickly

and completely as the memories of an Alzheimer's patient. That's because

despite Itzhaki's nearly 20-year struggle to get her work noticed, an

entrenched Alzheimer's research establishment remains skeptical. Worse, she

now finds herself on the brink of having to shut down what may be the most

promising avenue of investigation in ages.

" Our remaining funds are sufficient for only several more months, " she says,

" so unless we obtain a donation or grant, the work will then stop

completely, because nobody else in the world is directly doing such

research. "

For young men like Rich P., who wonders what's in store for him in the

decades ahead, this would appear to be an enormous scientific misstep ‹

particularly since Rich believes he's seen firsthand the link between herpes

and Alzheimer's.

His girlfriend's father, the one who passed away from Alzheimer's? He

battled cold sores all his life.

Itzhaki says there are two reasons why herpes became a Virus of Interest in

the hunt for an Alzheimer's cause. First was the observation, almost three

decades ago, that a rare infection called herpes encephalitis affects the

same regions of the brain that Alzheimer's does. Like people with

Alzheimer's, encephalitis patients can be plagued by memory problems. (Read

about the latest research on the secrets of your brain and how to preserve

your memories here.) The other factor, she says, is the prevalence of the

herpes virus itself.

" Most people get it as children, " Itzhaki says. " It's in your saliva, and it

can easily be passed along with a kiss from a family member. " She says it's

not really that puzzling that most people who carry the virus never show

symptoms ‹ as she puts it, not everyone who's infected with a microbe is

necessarily affected by it. " It depends on the person harboring the virus, "

she says. " It's probably based on genetic factors. "

How might a germ you could have contracted from, say, a grandparent

potentially destroy your brain when you become a grandparent?

In the early 1990s, researchers, including Itzhaki, found evidence

suggesting that as we age, the herpes virus begins moving from its hideout

near the bottom of the skull directly into the brain (possibly because our

immune systems lose some bite). Indeed, one Journal of Pathology study found

the virus in a high proportion of postmortem brain samples taken from people

who'd died in their later decades, while it was absent in those from people

who'd died in youth or middle age.

What effect does the virus have when it reaches your brain? The short

answer: That depends. In certain people it seems to do much less damage than

in others; just as some of us never develop cold sores, some of us can have

the herpes virus inside our brains without any horribly ill effects. But

Itzhaki believes that in other people ‹ specifically those who carry APOE

e4, a gene form, or allele, strongly linked to Alzheimer's ‹ the virus is

not only reactivated by triggers like stress or a weakened immune system,

but also actually begins to create the proteins that form the plaques and

tangles presumed to be responsible for Alzheimer's.

If you're looking for evidence, Itzhaki can show you a stack of it. In two

studies, for example, she and several colleagues took brain samples from 109

deceased people ‹ 61 of whom had had Alzheimer's, 48 of whom hadn't ‹ to

search for any correlation between herpes, APOE e4, and Alzheimer's. Their

results: People who had both the APOE e4 gene and the herpes virus in their

brains were 15 times more likely to have Alzheimer's than people who had

neither. (The researchers also found, intriguingly, that people who suffered

from recurrent cold sores were almost six times as likely to have the APOE

e4 gene as those who didn't get cold sores.)

A decade later, Dr. Federoff, then working at the University of Rochester,

administered the herpes virus to four different groups of mice, each of

which had a different variation or absence of the APOE gene. He found that

in mice with the specific APOE e4 variation, the virus was slower to become

dormant than it was in mice with APOE e2, APOE e3, or no APOE gene,

suggesting that the virus could be replicating faster in the e4 mice. " The

results definitely suggest there's something different about having APOE

e4, " says Dr. Federoff.

Still other research shows the direct impact of HSV-1 itself. In 2007, a

study by Itzhaki and Wozniak found that infecting lab samples of brain cells

with the virus caused a buildup of the protein (beta amyloid) that's the

primary component of the plaque clogging the brains of Alzheimer's patients.

The same study also found a similar result in the brains of mice that had

been infected with HSV-1.

Then there was January's study in the Journal of Pathology. In it, Itzhaki

and Wozniak looked at brain samples from 11 deceased people; six had had

Alzheimer's and five hadn't. While both groups had plaques (not

surprisingly, the Alzheimer's group had far more) and evidence of the herpes

virus in their brains, there was a crucial difference in the concentration

of the virus: In the Alzheimer's patients, 72 percent of the virus's DNA was

found in the plaques, compared with only 24 percent that was found in the

plaques of the non-Alzheimer' s brains. Not surprisingly, all but one of the

Alzheimer's sufferers also carried the APOE e4 gene, compared with none of

the samples from the non-Alzheimer' s people.

Wozniak is confident that these last two studies point to the same

conclusion: " The results strongly suggest that HSV-1 is a major cause of

amyloid plaques ‹ and probably of Alzheimer's disease. "

Halting Alzheimer's

For Wozniak and Itzhaki, the next step is to test whether antiviral drugs

like Zovirax and Valtrex, both of which are used to shorten the duration of

cold sores, might alleviate or slow the progression of Alzheimer's. The pair

is seeking funding for two experiments with antiviral drugs ‹ one testing

them on mice, the other testing them on Alzheimer's patients.

" If the treatment is successful, it would stop progression of the disease,

rather than just stopping the symptoms, " Itzhaki says.

But that funding isn't likely to materialize if the rest of the research

community continues to dismiss Itzhaki's theory ‹ or ignore it altogether.

When I e-mailed Trojanowski, M.D., Ph.D., a respected Alzheimer's

researcher at the University of Pennsylvania, to find out his take on the

connection between Alzheimer's and herpes, he shot back a one-sentence

reply: " Do not know of any connection. "

When I pressed and asked him to take a look at two of Itzhaki's recent

studies, he was equally dismissive. " This is an old story, " he said, " so I

do not think there is much new news here. "

Even those more familiar with the research remain skeptical. " One of the

things we see a lot in science is relationships ‹ two things happening

together, " says Bill Thies, Ph.D., chief medical and scientific officer at

the Alzheimer's Association. " But they often turn out to be independent

events, or you can't tell which thing is causing which. It could be, for

example, that there's something about amyloids that attracts HSV. "

Wozniak says that the study he published with Itzhaki ‹ in which the herpes

virus caused amyloid accumulation in cells and mice ‹ refutes that

criticism. He also dismisses another critique ‹ that he and Itzhaki haven't

established the mechanism by which HSV-1 brings about that accumulation.

Again, he argues, this study indicates an increase in the enzymes that are

responsible for forming amyloid from its precursor protein, called APP.

" Surely, the mechanism is clear: HSV-1 causes an increase in these enzymes,

which in turn causes degradation of APP, leading to amyloid formation. " He

pauses, and then adds wryly, " It's interesting that people raise this

criticism when, until our research, no other underlying causes of amyloid

production linked to Alzheimer's disease were known. "

Itzhaki is more sanguine about the skepticism. " We've seen this before when

a virus or bacterium is suggested as the cause for a chronic illness, " she

says, noting the reticence people had when H. pylori was suggested as a

cause of ulcers and when the human papilloma virus was suspected as a cause

of cervical cancer. Both are now largely considered medical fact. " And the

Alzheimer's establishment is very conservative. "

town's Dr. Federoff agrees that in some ways the theory isn't

conventional enough to be embraced by many mainstream Alzheimer's

researchers. " Herpes is a common virus, but in this case we're talking about

it behaving in an atypical way, " he notes. That said, would he like to see

further research on the connection between HSV and Alzheimer's? Absolutely.

There is one matter on which the opposing camps agree: With each passing

day, the stakes for Alzheimer's research grow higher. Over the past century,

the only thing that has prevented the disease from becoming even more

widespread and devastating is that most people passed away from something

else before they were old enough to develop it.

Drop dead of a heart attack when you're 52, and Alzheimer's is one malady

you probably won't have to worry about. (Actually, your biggest health

worries are probably less of a risk than you think. But you should watch out

for these six threats.) But the more progress we make against our most

common killers ‹ heart disease, stroke, and cancer ‹ and the more we extend

our life spans, the greater the number of Alzheimer's cases we're likely to

see. Indeed, as the 33-million-plus- strong baby boom generation enters its

golden years and sees its risk of Alzheimer's increase, we are potentially

looking at an epidemic. By 2010, the number of cases is expected to have

increased 10 percent from its 2000 total, and from there the number is

projected to more than double ‹ to more than 950,000 new cases a year ‹ by

2050.

" Alzheimer's has always been a big problem, but it's going to be even

bigger, " says Thies. " And the people who are now in their 20s, 30s, and 40s

are the ones it's especially going to affect. "

So what do you do if you're part of that group ‹ especially if you tend to

develop cold sores? One future option could be to have yourself tested for

the APOE e4 gene ‹ though Wozniak isn't a fan of that idea. " It would just

cause a lot of worry for the person involved and his or her family. "

Another possibility might be to take an oral antiviral drug preventively ‹

essentially, to attempt to keep the herpes virus in check before it can do

any damage to your brain. The hitch here, however, is that no clinical

trials have ever evaluated the safety of taking a daily antiviral, such as

Valtrex, for longer than a year. Plus, the average physician would consider

the link to Alzheimer's too tenuous to let you play guinea pig.

In the end, the best option may simply be to wait, and hope. When I ask

Wozniak whether he and Itzhaki feel like they're running out of time, he

says, " Of course. We are all getting older. Our parents are getting older.

Soon we'll all be affected one way or another by Alzheimer's disease... if

we haven't already. "

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