The Tangled Neuron

Chlamydia Pneumoniae and Alzheimer's

Summary: Infection with a common bacterium called Chlamydia pneumoniae may increase the risk of developing Alzheimer’s. The bacterium has already been linked to heart disease and hardening of the arteries. Work to investigate the role of viruses and bacteria such as Chlamydia pneumoniae in chronic diseases is in the early stages, but researchers hope it will help identify and treat the underlying causes of Alzheimer’s.

More study is needed to confirm the bacterium’s relationship with dementia, and rigorous clinical trials would be necessary before any treatments based on this research could be recommended.

I’ve written before about how viruses and bacteria can contribute to chronic diseases not previously linked to infections. It is now accepted that a type of bacteria contributes to ulcers, and that human papillomaviruses are the major cause of cervical cancer. A common bacterium called Chlamydia pneumoniae (also called Chlamydophila pneumoniae and C. pneumoniae) has been linked to atherosclerosis (hardening of the arteries) and other chronic diseases.

Dr. Brian Balin, a professor at the Philadelphia College of Osteopathic Medicine and Basic Science Director of the school’s Center for Chronic Disorders of Aging thinks that same bacterium may also contribute to many cases of Alzheimer’s. As the name indicates, the bacterium causes a type of pneumonia - it’s not the same as the sexually transmitted type of Chlamydia.

Although the link between C. pneumoniae and Alzheimer’s is not well-accepted, Dr. Balin has been researching the relationship for years. At a 1995 meeting he attended, talk turned to the possible link between the bacterium, hardening of the arteries and heart disease.

“I asked whether anyone had ever looked for the organism in brain tissue,” he remembers. “My background in neuropathology dealt with the blood brain barrier, and I had for some time believed that damage to the blood vessels in the brain could be involved in Alzheimer’s disease. My beliefs were not widely held….”

“Anyway, after asking the question, I performed a search of the literature and found that no one had ever looked in brain tissues for the presence of this infection.... So, I went to our -80 C freezers and pulled out frozen brain tissues from both AD [Alzheimer’s disease] and non-AD brains. I sent these samples in a coded or blinded fashion to Dr. Alan Hudson for analysis by polymerase chain reaction (PCR), which is a way of testing whether the DNA of the organism was in the tissue samples.” [Dr. Hudson is a Wayne State University School of Medicine professor whose lab focuses on Chlamydia research.]

It turned out that the AD tissue samples contained the DNA from the bacterium, while the non-AD tissues did not. The two researchers repeated the experiment with different samples, and got the same results.

“This then led to our expanded experiments to determine whether C. pneumoniae could be detected using a variety of methods,” says Dr. Balin. “All in all, we used six different techniques which gave consistent results. The first publication of our work was in 1998 in Medical Microbiology and Immunology.”

Chlamydia Pneumoniae - An Elusive Bacterium

All these different testing methods were necessary because Chlamydia pneumoniae is the Loch Ness Monster of the bacteria world – hard to categorize, and even harder to find.

“Because of the nature of this organism, one cannot take a ‘quick and dirty’ approach to this problem,” says Dr. Balin. The bacterium is hard to categorize because it acts more like a virus than a bacterium, growing inside cells and using the resources of the cell to reproduce. Even worse, he says, it keeps changing form. “C. pneumoniae has multiple developmental phases in its life cycle and expresses genes and proteins variably depending on things such as life cycle, environment, and tissue in which it is located.”

This may be why some labs report they have not found C pneumoniae in Alzheimer’s brains. But Dr. Balin thinks the extensive testing he and his colleagues have done is accurate. “There are a number of techniques used to detect C. pneumoniae in clinical samples… What we do, and which is not consistently done in other labs, is use multiple techniques with many different types of probes to detect the presence or not of C. pneumoniae in a clinical sample. We have used at least 15 different antibodies specific either to Chlamydia genus or Chlamydophila pneumoniae on our brain samples to determine if antigens from the bacterium can be detected in the tissues. In addition, multiple PCR primer sets have been used to detect different genetic sequences of C. pneumoniae. We also have used biochemical techniques, electron microscopy, and tissue culturing to demonstrate C. pneumoniae in brain samples. We believe the most thorough sampling is required to truly rule in or rule out presence of the organism in brain tissues.”

He received some confirmation of his findings this year, when scientists at the Wroclaw Medical University in Poland reported finding Chlamydia pneumoniae in the spinal fluid of 44 percent of the Alzheimer’s patients they tested, but only 11 percent of a control group. The Polish researchers suggested that testing for the bacterium in spinal fluid could be useful in the diagnosis of Alzheimer’s.

How Chlamydia Pneumoniae May Trigger Alzheimer’s

How could a type of pneumonia affect the brain? “My group has found that C. pneumoniae, once inhaled, infects white blood cells, in particular the monocytes that circulate throughout the blood stream,” Dr. Balin explains. “These cells can enter through the walls of the blood vessels and can carry the organism into different tissues, including the brain.”

“We also have evidence that the cells in our upper noses known as the olfactory neuroepithelial cells (those cells controlling our sense of smell) are infected by C. pneumoniae.” The olfactory neuroepithelial cells are close to the olfactory bulb region of the brain and to the hippocampus, where short term memory is formed. These areas of the brain are among the first to be affected by Alzheimer’s. This suggests there may be a link between infection with C. pneumoniae and the reported association between the loss of sense of smell and the onset of Alzheimer’s.

Finally, there is some tantalizing evidence that the bacterium may actually trigger the formation of the amyloid plaques characteristic of Alzheimer’s brains. When mice in Dr. Balin’s lab were infected with C. pneumoniae, they developed amyloid plaques in their brains. Adding to the evidence of the link between the bacterium and Alzheimer’s pathology, the bacterium was found near plaques and tangles in human Alzheimer’s brains studied in his lab.

C. Pneumoniae – Another Piece of the Dementia Puzzle?

Dr. Balin points out that the connection between C. pneumoniae and Alzheimer’s is consistent with other research on the disease. Some scientists think inflammation causes the brain damage seen in Alzheimer’s. “Quite possibly the inflammatory response due to a chronic persistent infection with C. pneumoniae and/or other infectants causes much of the cellular damage in the brain,” he says. “Also, genetic risk factors such as having the ApoE 4 variant which has been correlated with Alzheimer’s disease may actually increase one’s risk for being infected with C. pneumoniae and other infectants such as Herpes Simplex Virus 1. The interrelationship of ApoE with infectants may be how this variation confers greater risk for getting both infections and Alzheimer’s disease. Our data have shown that Alzheimer’s brains that express the ApoE4 variation actually have greater concentrations of C. pneumoniae than Alzheimer’s brains not expressing the variant.”

He thinks the connection between C. pneumoniae and hardening of the arteries may also be relevant to dementia. Of course, arteries are a type of blood vessel. Once white blood cells infected with C. pneumoniae reach the brain, Dr. Balin theorizes, they may damage the blood vessel walls there. This would contribute to vascular dementia and brain tissue damage.

But if exposure to Chlamydia pneumoniae is common, as indicated by the antibodies in many people’s blood, why don’t we all develop Alzheimer’s? “Exposure to an infectious agent does not necessarily translate into a specific disease,” says Dr. Balin. “There are many other factors, both genetic and environmental, that would dictate why some get a disease and others do not, even when you have a large percentage of the population exposed to the infectious agent. One example is exposure to the common cold viruses, which are very ubiquitous. Not everyone exposed gets a cold. …so, not everyone exposed to C. pneumoniae would develop Alzheimer’s, but the potential for the disease would be ever-present.”

Potential Treatments for Alzheimer’s and Dementia

Dr. Balin cautions against rushing to treat Alzheimer’s based on the possibility that C. pneumoniae could trigger the disease. “The dilemma that we face is that without current long-term effective treatments for AD, many people may want to try, even experimentally, other types of drug regimens based on the work that we and others are doing with infection,” he says. “Obviously, without clinical trials first, we cannot know for sure who would be most likely to benefit. We have to determine who is infected with which organism(s) and try to treat appropriately. This is why we really need a concerted effort to develop controlled clinical trials.”

He’s done some thinking about what types of therapies a clinical trial could test. “We know that Herpes Simplex Virus 1 may be involved in a significant number of AD cases and this may also have to be considered in a therapeutic regimen. All in all, I think that infection data (even at this point in time), suggests that using combination therapy of an anti-inflammatory, anti-chlamydial and an anti-viral for Herpes could be beneficial."

The “cocktail” he is proposing for trials includes anti-inflammatory medicines or NSAIDs (non-steroidal anti-inflammatory drugs such as aspirin and ibuprofen). Although some population studies have shown a link between NSAID use and decreased risk of Alzheimer’s, evidence from clinical trials using NSAIDs to slow progression of the disease is not very encouraging. If inflammation is caused by infection with C. pneumoniae, Dr. Balin says, it’s unlikely that it could be controlled in the long run by NSAIDs alone.

Antibiotics targeted to Chlamydia bacteria are also part of the proposed cocktail. At least one study has shown antibiotics may slow progression of mild to moderate Alzheimer’s, but more research is needed. “Our research suggests that treating individuals who have Mild Cognitive Impairment, and those who have newly diagnosed and/or existing Mild AD, with anti-chlamydial antibiotics may have a positive effect by either stopping a trigger for the disease or preventing disease onset in the case of MCI,” Dr. Balin says.

But antibiotics don’t always wipe out C. pneumoniae, and as with other infectious disease, there are worries that the bacterium will become resistant to treatment. These worries have scientists searching for alternative therapies, Dr. Balin says. “The use of more novel anti-infection compounds, and potentially the development of a vaccine for these infectants could result in combating dementia-causing organisms.”

Hopes For Finding And Treating The Causes Of Alzheimer’s

“I believe that we have uncovered a non-conventional infectious agent that likely is
increasing the risk for the development of Alzheimer’s,” Dr. Balin says. “We don’t yet have all the answers. However, there is hope because we are still discovering and studying how this actually works. Similar to how the discovery of a bacterium is the cause of gastric ulcers and some types of gastric cancers, we are hopeful that our findings result in expanded efforts by others to consider how infection may be causing many diseases in the nervous system not currently considered to be infectious. This understanding is vital to proceeding in a rational fashion to treat the problem based on the evidence. This will take us from simply trying to treat the symptoms of disease to actually treating the causes. This is why I have great hope that we will defeat this and other neurodegenerative diseases in our lifetimes.”

Dementia Caregivers Share Their Stories: Book Review

Bernie Cavis, Director of Dementia Product Line Management at Brookdale Senior Living, gave me a copy of Dementia Caregivers Share Their Stories: A Support Group In A Book. I’m fascinated by the stories in this book. The caregiving experiences of the authors, Lynda A. Markut and Anatole Crane, are woven in with those of the twenty-six families interviewed.

In May, I found Lynda browsing the displays at the Wisconsin Conference on Alzheimer’s Disease and Related Disorders. She is Education and Dementia Care Specialist at Family Care Alliance Inc., a not-for-profit geriatric health facility in Illinois, and consults on the specialized care needs of persons with dementia. She also is an adjunct professor at McHenry College, where she teaches Introduction to Gernontology, an upper level psychology course.

Lynda Markut, M.S., L.S.W.

Both of Lynda’s parents had dementia, she says. “My father died twenty-one years ago from a dementia we now think could have been normal pressure hydrocephalus. We weren’t quite as sophisticated as we are now, but given his symptoms, we think that’s probably what he had. My mom had vascular dementia with complications from uncontrolled diabetes.”

She tells me that her co-author was caregiver for his wife Martha for fifteen years. Anatole, a microbiologist, began attending a general support group at Family Alliance shortly after Martha was diagnosed with probable Alzheimer’s at fifty-three. He also helped Lynda start a well-spouse support group.

“Anatole and I would talk about the fact that there was no book out there that told caregivers what families do right,” Lynda says. “And the books were usually written by professionals. We talked about having a support group in a book - families could pick it up at any time and check out what other families might have gone through or had done about a particular situation.”

They brought this idea up in their general support group, and members agreed to be interviewed for the potential book. “As we interviewed the family members, they came to realize all they had done,” she says. “For the first time, they acknowledged their accomplishments. If the book had gone no further, it would have been a success.”

But it did go further. “We had the interviews transcribed; then we started to write. We rewrote it a number of times until we realized the strongest statements would be made by the caregivers themselves. So, we set about letting the caregivers speak, and Anatole and I wrote the transitions.”

Because Lynda had been facilitating support groups for over twenty years, it came naturally to organize the book like one of her groups. “We started with the diagnosis and worked through caregiving issues, emotions, etc., all the way to the terminal stage of the illness,” she says.

The caregivers in the book wryly acknowledge the difficulties of caregiving: family disagreements, their sense of loss, dealing with embarrassing behavior and caregiver burnout. They matter-of-factly chronicle how their lives changed, and what solutions worked for them.

But the essence of the book is the life stories of the twenty-eight families. The stories are vivid and rich with detail – as much about gardening, music and family life as they are about memory loss, personality change and toileting.

Maybe it’s because the people in the book are looking back instead of narrating from the middle of a caregiving crisis. Maybe it’s because they had access to the support services they needed. Maybe they’re just an extraordinary group of people. Whatever the reason, their voices are full of quiet satisfaction and a sense of accomplishment. We can all benefit from their vision of dignity and growth through caregiving.