Alan MacDonald, M.D., is a pathologist affiliated with St. Catherine of Siena Medical Center in Smithtown, New York. His current research is concentrated on developing what he refers to as a new biology for Lyme disease, including the use of special DNA probes to detect Borrelia DNA in spinal fluid and in tissue sections from Alzheimer autopsy tissues.


Through his research, and with the help of other leading researchers in the field of molecular and cellular biology, Dr. MacDonald is pioneering a broader understanding about the behavior of Borrelia burgdorferi, the bacteria that causes Lyme disease. He has appeared as an invited lecturer at Lyme symposia, including the ILADS National Scientific Meetings and Columbia University/Lyme Disease Association conferences in Philadelphia, PA, where he presents the findings from his explorations into the connection between Borrelia spirochetal infection and Alzheimer's disease.


Dr. MacDonald initially began working with the model of Lyme disease and pregnancy, and had developed techniques to identify the spirochete in tissue, from either biopsy or autopsy tissues, and applied those techniques to the study of the fetuses. He was then able to transition from pathology to studies of brain tissue. His interest in Alzheimer's disease and Lyme began when attending a Lyme disease conference in Vienna, Austria. The speakers were describing Lyme disease as having three stages: primary, secondary and tertiary. Since those terms are also used to describe syphilis, it occurred to him that if Lyme disease had a tertiary, late-stage form, perhaps the late manifestation could be dementia. Like syphilis, which also had late stage dementia, Lyme disease may reoccur thirty or forty years after infection. He hypothesized that if there is a dementia occurring in late-stage Lyme, it might be an Alzheimer's-like illness, a late manifestation of bacterial infection in the brain.


Dr. Alan MacDonald:
"Using the syphilis model, I began to study some autopsied brains, and found that I was able to identify spirochetes in autopsied brain tissue in the hippocampus, which is one of the areas that Alzheimer's disease tends to target in every patient. I was able to grow spirochetes from autopsied Alzheimer's brain tissue, and stain the spirochetes with special monochromal antibodies, through the techniques I learned and developed through the study of stillborn babies with Lyme disease. And those two positive results made me think even more strongly that some Alzheimer's might be like syphilis, a late manifestation of the bacterial infection in the brain, not to say that all Alzheimer's disease is related to Lyme disease, but some.

Over the years, I had carried that theme a little further, and done some more work, and thought more about it. I tried to establish ways that we could make connection between the pathology findings of Alzheimer's disease and a spirochetal infection in the brain, which moves from the hippocampus to the higher memory centers in the brain. I had some success with that line of reasoning in 2004, 2005."

Dr. MacDonald delivered a summary of his research findings at a Philadelphia, PA meeting of the LDA Lyme Disease Association and ILADS. That lecture and accompanying images is accessible through Dr. MacDonald's website:
http://www.molecularalzheimer.org.

"So, using the microscope, and using the model of syphilis I was able to develop some ideas and test the hypothesis and get some encouraging, positive results," he says.


Case Study: Paul Christensen

One of Dr. MacDonald's most exciting research results comes from a uniquely well-documented case of one man who passed away from Alzheimer's disease, Paul Christensen, and was autopsied at Stony Brook in Long Island. A firefighter, Christensen was diagnosed with Lyme disease when the Borrelia bacteria was found in his spinal fluid. He was treated for a short time by doctors at Stony Brook University Hospital and then released. However, his diagnosis of Lyme was followed by an eight year period of mental deterioration, and he ultimately died from Alzheimer's disease.

Christensen's wife, in an effort to support and encourage Dr. MacDonald to help educate the medical community about the connection between Lyme and Alzheimer's disease, contacted him and allowed him access to study Christensen's brain tissue for clues about this connection. Dr. MacDonald was "able to show that those areas of Alzheimer-type injury in the brain also lit up for spirochetal DNA, with special florescent dye attached to the DNA probe."

Through his work in the thoroughly researched, well-evaluated Christensen case, which he confirms has been one of the most exciting cases he has worked on, Dr. MacDonald learned that using DNA probes allowed him another point of reference in order to show the spirochetal DNA in the brain tissue, and therefore, "make the connection between Lyme disease and Alzheimer's in some patients," he says.

The Canadian Lyme foundation has a number of links to my work, and also has published the case of Paul Christensen on their website:
http://www.canlyme.com.


How is Alzheimer's disease treated?

"Alzheimer's disease is treated with comfort care. They give patients support, but don't use any antibiotic treatment. They give treatment to prolong the survival of some of the neurotransmitters of the brain, such as Aricept. These medicines help to prolong periods where patients can have some functional independence. But it does not slow the disease down, or shorten the disease."


How commonly known is your research, and the link between Alzheimer's and Lyme disease?

"The people who attended the symposia that were held in Philadelphia and those who know about ILADS would probably know about my work. I don't know if everybody who sees patients know about my work. It's probably more likely that people in the northeast will know about it. You can do a Google search for
Alzheimer's and Borrelia, you'll find my papers on the Internet. You'll also find papers from people who dispute the connection as well, but it's in the public domain for people to look at."



What is the spirochete and what does it do?

"People think of the spirochete as the spiral form, corkscrew shaped form, and that is what you'll read about if you look in a biology or medical textbook. You'll see that spirochetes are different from other bacteria because they are long and curly. They expect to see that when they look in tissue.

Unfortunately, spirochetes have more diverse forms than just the corkscrew, or spiral form. One of the functions of my website is to call attention to the other forms that exist that are just as legitimate as the spiral form. If you took the spiral and you reduce it to dashes and dots, those little dots contain DNA, and those are smaller units of the spirochete. There are also rounded balloon-like form called the cystic form. Spirochetes in certain circumstances will round up and make a round balloon-like structure, which has its DNA, and that is a second form. And then there are a number of very easily distorted forms called L-forms, which are sort of like soap bubbles that can stretch out and contain various boundaries, and are not as easy to identify as spirochetes, but they are also a part of the mixture of forms that the spirochete can have.

One of the functions of my website is to call attention to the fact that not only is this true for the Borrelia spirochete, but it's true for the syphilis spirochete, its related morphology, or shape changes are common to the two.

If you're looking for evidence of an infection in tissue you want to see the bug. And if you're looking for the bug and you only look for spiral forms, you may miss the other forms, forms that are granular or rounded cyst forms or L-forms."


Research yields discovery of Borrelia biofilms

"One of the most exciting things we've come across in the last six months is the idea that, in addition to all these forms, there are groupings of spirochetes, or colonies, that are biofilms. Biofilms are one of the things that bacteria use to promote their survival in adverse conditions.

We've shown, in our preliminary work, Dr. Eva Sapi and I, that Borrelia biofilms are part of the biology of Borrelia. And that these biofilms are ways or strategies for spirochetes to survive in hostile or adverse conditions.

In the biofilm unit, which is a colony of spirochetes, the spiral form is often lost and is replaced by cystic forms, granular dot forms, or L-forms. So that makes all of the previous biological discussion that I've just reviewed very relevant, and very meaningful. It helps to understand that a group of spirochetes with the DNA and the potential to cause disease can exist without having a single spiral form at all, but they have other diverse forms as they unite into a colony to survive under adverse conditions.

Biofilms are very resistant to antibiotic treatment, and they are resistant to killing, and we've found biofilms in cases of European Lyme Borreliosis, which is the skin manifestation: Acrodermatitis chronica atrophicans (ACA).

Studies that have been done in Europe have shown that colonies of Borrelia spirochetes are present in the skin, and people have had a condition called acrodermatitis chronica atrophicans (ACA), a condition where the skin gets very thin and very fragile, and it persists for many years, and is one of the late manifestations of Lyme disease in the skin. It occurs about thirty years after you've been infected. It's associated with the European form. It isn't very common over here. At least people don't think it is.

ACA contains groupings or colonies of Borrelia, and we have shown that those groupings or colonies are actually Borrelia biofilms. Biofilms are one of the ways that bugs survive in a hostile environment for long periods of time in nature, or in the human body, or in niches where they want to establish themselves."

Hostile environments to the bug are the body's immune system and antibiotics?

"Yes, all those things are hostile to the bug, and the bug then pulls out its bag of tricks different things to help it survive under those conditions. Most of the antibiotics we have today in medicine are derived from soil bacteria. People will go around the world and collect samples of soil and they'll grow the bugs, and they'll look for new antibiotics produced by those bugs, or actual chemical products that interfere with the growth of other bacteria. So, antibiotics are usually derived from bacteria designed to kill or suppress other bacteria in their immediate environment.

So, it makes sense that biofilms would produce substances that create a hostile environment for other bugs in the general area where the biofilm is, so that only the bacteria inside the biofilm are able to survive, and do their biological functions.

They've shown that the resistance inside the biofilm to antibiotics that might be coming in from the outside is markedly increased, and bugs that would normally be killed by one unit are not killed at all, and they might not be killed by a thousand units as long as they stay inside the biofilm, which is like a gelatinous wrapping around colonies of bugs which keep the antibiotics from getting into the center to kill the bugs that are there.

Biofilm looks like a film, and it has potential to protect the bugs inside the film from outside hostile environments, including antibiotics."


A new biology for Lyme disease

"So, all of this is very, very relevant to how we think about a 'new biology' for Lyme disease. If you boil down everything that I have tried to do in my career, it comes down to making a case for a new biology of this bacteria. A biology which includes various forms, various groupings or biofilms, survival of these bugs inside the human body, both inside cells and outside of cells, and the longterm capability of these living organisms to create diseased conditions of various types in the human body, just like syphilis did when it was a major public health problem.

Syphilis could involve any organ system in the body. When people in the 17th, 18th, 19th century had syphilis, they would not all get the same medical conditions, they would get a variety of medical conditions. And they would not all get the same neurological conditions, they would have a variety of conditions. And one of them was dementia, which was called General Paresis.

Variability of the bug, variability of the infection in the organ system, clinical symptoms, and variability of outcomes is just one of the things that makes syphilis a very interesting infection to study, and makes Borrelia very interesting to study, using that model to help us think about how Borrelia can cause problems in the human arena.

So, the research makes for very interesting reading, and it gives people an opportunity to relearn from the model of syphilis, reacquaint themselves with the diversity, the variety, the difficulty in treating and curing syphilis. Many of those things are very similar to the problems we face in understanding and trying to treat and cure Borrelia infections in this century. It's not much of a leap, it's just a sidestep."

Lyme is generally thought to be passed on through ticks, however there are other means. How is Lyme disease passed on?

"It can happen through 'vertical transmission' from mother to fetus, and it happened in syphilis. It does happen in certain people who have Borrelia infection. It goes across the placenta and can cause trouble in the fetus. That autopsy work I did, way back in the eighties, has been published and is out there for people to look at."

What's the difference between active Borrelia infection and dormant infection?

"It might be thought of as infection causing tissue injury. So, as the infection is in the body in any of its forms, and the person who has that infection experiences tissue injury, that is active infection, as opposed to dormant infection, where the infection is in the body but doesn't cause any tissue injury, and the patient doesn't have any symptoms, but because it's in the body it has the capacity to reactivate at a future time. That's how you get across a twenty, thirty, forty year period, to late tertiary manifestations. People may have dormant infection that don't flare up again until late in life, when the immune system, or other factors allow that infection to reactivate.

One of the best examples of that is shingles. People who have had Chicken Pox as a child at age five can have, late in life, reactivation of that virus that's been in the body in a dormant form, and then blisters in the skin will develop in their sixties, sixties, seventies, or eighties, and they'll have a reactivation of that viral infection which entered the body when they were five years old. And it's an example of a dormant or latent infection in the body which only flares up many years, or decades, after it entered the body.

Syphilis can do that, Borrelia can do that, Chicken Pox can do that, other infections can do that. So it's not a controversial topic. It's only controversial when you apply it to Lyme disease. People don't like to put that together with Lyme disease, but it is a very reasonable and very valid association that infections can reactivate."


In your view, why is the recurrence of Lyme infection controversial?

"We live in an arena where there are political, as well as scientific and medical discussions. And I think that scientific and medical discussions are important, and political discussions sometimes prevent us from getting very far with our science and our medicine. As long as people enter an opportunity for discussion and dialog with preconceived notions about what they will and will not embrace as an idea, you have a political weight that is dragging down the level of the opportunity to learn from discussion or from listening to patients.

If people decide that there is no such thing as maternal fetal transmission in
Lyme disease, then they can't learn very much when they read my paper, because my paper does show that there is tissue evidence of the infection in newborns that were stillborn, or fetuses that didn't make it to full term.

And there are opportunities to read other papers and not understand how dormant conditions can exist for twenty or thirty years, such as the ACA model in Europe. If you enter the discussion with a preconceived notion of what you will or will not take away from the discussion, you can't learn. So politics is an unfortunate mindset, where the mind is closed before the discussion begins. And that's where a lot of, I think, the politics of discord come from in discussing this, or any other infection.

You know, in the early days of HIV infection, there was a certain reluctance to see it as a public health problem that we know now HIV infections are, in a worldwide basis. But back in the early eighties, when I was beginning my practice, there wasn't a lot of open mindedness about the need to treat HIV as a medical problem. It was a political problem for people who came from Haiti, or for people who lived in San Francisco who happened to be gay. It was a political problem.

Now, we have gotten past that and we see that HIV is a chronic infection. It's a medical issue, not a political issue anymore. Sometimes it takes a long time for politics to exit, and for medicine and science to get back on an even keel."


How long might it take before Lyme becomes less political and more of a medical issue?

"Well, we want to learn from every patient that we can. When Dr. Alzheimer was alive, he wrote about two people with the disease. His first patient was a woman, August D. Then later, before he died prematurely, but he died. Shortly before that he had written about another case history from Alzheimer's.

Now, two cases do not make a very satisfactory platform for describing a new public health epidemic of dementia, which is what we face today. But at the time of Alzheimer's life, there were only two cases. So, sometimes offer a platform for us to understand a problem major public health problem in every continent on this planet.

So sometimes new ideas which emerge from the study of one or two or three cases offer a platform for us to understand major public health problems. So, carefully studied cases, even though they're small and they don't have a lot of statistical weight, sometimes do help us to understand, if you're allowed to think without politics getting in the way of thinking, and clouding your vision."


Where is your research taking you now?

"I'm using DNA probes now, I think that antibodies are very good, but antibodies don't have the great precision that DNA probes do. So I'm using DNA labeled with florescent dyes to eevaluate biofilms of Borrelia to evaluate tissues of those who have died from Alzheimer's. I'm going to use those probes to identify patterns of infection in those two categories: The biofilm category, which is the grouping of the colonies of the bacteria in test tubes or in human tissue, and the Alzheimer work of course, to take autopsy brain tissue, and evaluate that with the DNA probes, to see where the probes light up, and to see if we can find more like Mr. Christensen's case, lit up those Alzheimer's plaques, or those rounded areas of injury in the brain, and develop a larger series of cases to present to the scientific and medical community."

[Please note: Go to
www.molecularalzheimer.org, for pictures, research papers, lectures, as well as podcast interviews which he has conducted with Clinical Neurology News, where he discusses the research results as well as the reasoning behind his research. Dr. MacDonald will be speaking at the University of New Haven in May, presenting his findings regarding biofilms of Borrelia with Dr. Eva Sapi, another leading researcher in the area who has some very interesting work to tell us about.]

Dr. MacDonald, thank you for talking with us about your work

"I hope that some of this research will pay off at the patients' medical visits or at the bedside of the patient in the hospital. That's the goal of research, to make a difference in how people are evaluated and treated. And if some people can benefit from Lyme research, and Lyme mimicking Alzheimer's disease, then I think the research will have fulfilled its purpose, which is to try to find a group of people who could benefit from antibiotic therapy, and not go on to die from Alzheimer's disease. That would be a wonderful opportunity.

Thank you so much, and all good wishes."

Dr. MacDonald's website is http://www.molecularalzheimer.org. Go there to see images from his research, and find links for access to his research papers and further information about his work. He spoke with us about the significance of his research on April 6, 2008.