Part 1
by
Thomas Grier

Two Ends of the Same Spirochete

How Dr. Judith Mikklossy and Dr. Alan MacDonald approached the role that Borrelia play in Alzheimer’s Dementia from two different perspectives. Dr. Mikklossy looked at the initial disease formation and the effects of Borrelia on Brain-Cell-Cultures, Dr. Alan MacDonald looked at the end process of this infection by observing borrelia in Brain autopsies from Alzheimer’s patients.

I first started becoming seriously ill in 1989 and by the Spring of 1991 I was diagnosed with Multiple Sclerosis. After months of despair at the lack of concern by my physicians, I finally collapsed in the street. I was unable to walk, drive, read a book, or control my body contortions.

I was sent to the neurology ward of the closest hospital St. Luke’s. This hospital employed different neurologists than the clinic where I had been doctoring for two years. I had poorly controlled atrial fibrillation, an enlarged heart, severe pressure in my head, and a visual field where my eyesight was reduced to a fuzzy disk with completely distorted peripheral vision. I was racked with pain, fevers, sweats, and was having both auditory and visual hallucinations.

The doctors were at a loss. What had been considered as Multiple Sclerosis was now an unknown mystery disease.

After a week waiting for answers to various tests, I was put on a waiting list for a nursing home. My doctors gave me nothing but dire news of my prognosis. My personal family doctor and the neurologist I had been seeing were on vacation all week. (This turned out to be a blessing.)

I entered the hospital on a Friday and by Monday I had not seen any take charge doctor. After three days of being bed ridden and given supportive care by well-meaning nurses, the on-duty neurologist that saw me, visited me Monday morning and looked bone tired. This was the first time Dr. Barbara Martyn had ever seen me. (I had been diagnosed at the clinic across town with “MS” for over a year and had seen dozens of doctors and a half dozen specialties at a cost of over $100,00)

This doctor had seen me all of 10 minutes and suggested to me that I did not have MS but rather that I had Lyme disease. She ordered that a 20 day course of intravenous Rocephin be started immediately. But she also continued with the MS tests that had been ordered over the weekend.

I was told there was a long wait to get a brain MRI. Out hospital patients had a four month wait and in-hospital patients had to wait 10 days. Within a few hours of seeing this doctor I had both a CAT-Scan and an MRI.

Dr. Martyn MD (Now deceased from breast cancer) had over the weekend been attending the International Lyme Disease Conference in Arlington Virginia, and only had 4 hours sleep because her flight was delayed. Yet because of that conference she was able to look at my chart and in five minutes decided that Lyme disease was now the most likely cause of my multitude of multi-systemic maladies.

But all of this is a story for another time.

My misdiagnosis with Multiple Sclerosis galvanized my commitment to learn more about the spirochetal disease that was literally swimming inside my brain. As a graduate student 10 years earlier I had worked at the next door specialty hospital and worked with a Tertiary Sphillis patient that had failed three attempts of ever increasing doses of IM Penicillin. So having spirochetes in my brain was not a comforting thought.

Through my association with a Nurse Educator (Barbara Jones RN, MS) it became clear to me in 1991 that other MS patients just like me also had been misdiagnosed and actually had Lyme disease. I felt that what I was experiencing, felt like an infection of my brain, but it also manifested much like dementia.

I could not think clearly. When I spoke I now substituted easy words for hard words, reading black text on white paper gave me seizures, I got lost easily, I was both seeing and hearing things that weren’t real. Emotionally it was like I had a lobotomy that had cut all the feeling out of my brain. I had intellect, but no emotions. Other than uncontrollable urges to cry, I felt as though I had no emotional contact to the world.

That first day of antibiotic therapy, the IV Rocephin caused every muscle in my body to twitch and my body to spasm. The pressure in my head doubled, my entire body perspired and I spiked high fevers. It was this first few hours of agony that I became committed to better understand Lyme disease, and its affects on the human brain. At this time I did not know that my decades of running in the woods and meadows had exposed me to many tick-borne diseases.

As part of my journey I attended every medical conference that I could get to, and by 1997 I had attended well over a dozen conferences, and I tried my best to make sense out of what the CDC and Yale Medical were reporting: It didn’t make any sense?

I kept asking myself “Where are the pathology studies? Why aren’t they looking in the brain.”

I didn’t know then that human pathology studies would never be done with any American tax-payer dollars, and that the CDC and NIH would shoot down all requests for brain-autopsies done in America that would look for spirochetes in the brain.

My first encounter with the CDC hiding information:

I had been a graduate student at the U of MN School of Medicine for two years, and after I was able to walk again. (I didn’t drive much for the next five years) I visited my old mentor at the Medical School to talk to him about this misunderstood disease. Dr. Eugene Cotton was the head of the medical school, and he immediately became enthralled with what I was saying.

I was a Lyme patient who could speak to him in medical terms of what I was going through and explain the odd contradictions that I was encountering with medical experts. Gene immediately spoke up. His friend was the head of the CDC and he had just seen a study by Dr. Judith Miklossy that showed the presence of Borrelia burgdorferi in the brains of 13 consecutive Alzheimer’s patients in Switzerland.

He was so concerned with these findings that he ordered a brain-autopsy study to be done with American dollars, but that the work be done in secret in Canada and no results to be published or reported without going through the CDC.

No results were ever released.

So I called the graduate assistant to the doctor and was met with nothing but hostility and his repeating that all results were proprietary and were never meant to be pubished.

WHAT? We paid for this study! What good is a public health study if the results aren’t shared with the medical community?

Miklossy J, Kasas S, Janzer RC, Ardizzoni F, Van der Loos H. Further ultrastructural evidence that spirochaetes may play a role in the aetiology of Alzheimer’s disease. 1994 Neuroreport. 2;5(10):1201-4.

How research on Lyme is hindered by poor science: It astounded me that all research conducted on animals used only strain B-31 a laboratory strain of Borrelia not found in ticks. More disturbing was that every far-reaching conclusion about diagnosis, and treatment success was based entirely on antibody serology tests created using lab strain B-13.

Over and over repeatedly these antibody tests had been proven unreliable and several published studies pointed out how nebulous these tests were and how flipping a coin was just as accurate. All conclusions about neuroborreliosis were based almost entirely on unreliable antibody-serology tests! Diagnosis was made by serology, and cure was determined by a drop in antibodies. No one at the CDC or major medical institutions seemed to have interest in cracking a few heads open and looking for spirochetes with better tools.

[See photo of testing failures]

The few incidents of culture positives in patient’s after receiving antibiotic treatment, were being purposely ignored and never acknowledged or referenced in papers by the CDC. By 1995 it was clear to me that when it came to the pathology of neuroborreliosis, the Lyme-patient community was completely on their own.

JUST LIKE MEDICAL ADVANCES IN THE 19TH CENTURY, INDIVIDUALS WERE NOW TAKING IT UPON THEMSELVES TO DO THE RESEARCH THAT THE PAID EXPERTS REFUSE TO DO.

In 1994 I had administrated an antibiotic treatment study in Pine County Minnesota for MS patients. I enrolled 26 MS patients diagnosed by both MRI and spinal fluid findings. We only enrolled seronegative patients using either the IGenix Lyme ELISA test or Marshfield Clinic Lyme serology tests. I insisted that only seronegative patients be enrolled and treated. I chose negative patients with clinical symptoms, because these were the patients that were slipping through the cracks in the medical system and not receiving treatment simply because the Lyme antibody tests were inaccurate.

We fell short of our goal of 40+ patients and a big part of that was I felt, the lack of cooperation by the MS Society. Not only could I not speak at their local MS Support Groups to enroll patients, but the MS Support groups would not even distribute our consent forms and brochure. One MS Support Group leader told me that all Lyme disease did was offer false hopes.

Most MS patients were told that Lyme disease had no connection to MS, and in one instance where I spoke to MS patients at the Houghton Michigan MS support group, the MS society flew out a representative one week later for a special meeting with the group, and she spoke very harshly to the support group who had allowed me to speak. Eight members of that group were so outraged that the very next month they splintered off from the MS support network, and formed the first Houghton-Hancock LDSG. After I spoke I arranged for a LLMD near Green Bay WI to treat any and all of the MS patients who could not get treated in Michigan. In all, eight of the MS patients had dramatically improved on antibiotics.

One of those patients enrolled in our LEAMS study (Lyme Endemic Area MS Study) and went from crutches to walking and made cognitive improvements to the point of renegotiating his divorce settlement and getting total custody of his kids. He even appeared on a local talk show and encouraged other MS patients to get treated with antibiotics. The backlash by the Upper Peninsula Health Department was swift and completely unyielding in their opinion that treating Lyme disease long-term or treating MS with antibiotics was a waste of time and dangerous.

Of the 26 MS patients in our antibiotic trial, only three seroconverted and had positive serologic evidence of having Lyme disease. But a total of 8 of the 26 patients overall responded favorably to three months of antibiotics. Unfortunately, 17 of 26 did not respond at all.

After a one year follow-up, we discovered that one patient in our treatment failure group had stayed on amoxicillin for 15 months and made a nearly total recovery.

What I concluded from our MS antibiotic treatment study was this:

• # of Patients Conclusion Length of Rx w/Amox/doxy/Biaxin
• 3 Had Lyme disease and made partial recoveries 3 months
• 5 5 patients had improvement but were not seropositive 3 months
• 17 Had no response to antibiotics either doxy/amox/or Biaxin 3-months Rx
• 1 One MS patient had 15 months of amoxicillin and made a near full recovery

I found the results disappointing and had hoped for better. My thoughts on our results are: Not all MS is caused by the Lyme bacteria, and that our treatment length was far too short. It would be years later in 2004 when Alan MacDonald would discover an association in MS with nematode parasites and that these parasites were often associated with Borrelia and found in the human brain in many dementia cases.

It may well be that as many as half the cases of MS and dementia are caused by mixed infections. Also we knew nothing of other Borrelia species like Borrelia myamotoi that also enters the brain, and is seronegative on lyme tests.

I was very frustrated. Our study was ignored by the Minnesota health department and they would not even consider a study of their own. When I presented my proposal to State Representative Mary Murphy, Dr. Michael Osterholm PhD the state epidemiologist crashed the meeting insisting that he talk with her alone. (She got very angry.) Osterholm said it was ridiculous to even report MS in surveillance reports because it wasn’t an infectious disease.

He also repeatedly said that hunters cannot get Lyme disease in the Fall because the female ticks won’t feed on humans in those months??? He made these comments because I had helped pass a bill to distribute Lyme information to hunters. Of course he lied.His own paper that he gave Representative Murphy stated that Lyme disease can be contracted in any month of the year and cases had been reported in all months in Minnesota.

It was clear that the State Health department wasn’t going to be any help in a human pathology Lyme Study. It was now 1995 and I had run out of medical sources to get for better answers and better studies? But this was the year that I met Dr. Alan MacDonald.

I first met Dr. Alan MacDonald (pathologist) at an LDF conference. Between talks he was carrying a small boy on his shoulders and he joyfully talked about creating a CD-ROM of various forms of spirochetes and pontificated about the role of variant forms. Almost simultaneously we remarked on the extraordinary work by Dr. Gabriel Steiner in Germany and his findings of “crescent-like” forms in the brains of MS patients.

As luck would have it Dr. Vincent Marshall the expert on Gabriel Steiner was at this conference and his insights on spirochetes in the human brain in MS patients were invaluable to me.

No one else in America had been looking back 75 years in the European Literature for a spirochete connection to MS. While it is easy to dismiss any one published study on MS and spirochetes, it is complete denial to dismiss over 30 pre-WWII published studies by a dozen different researchers in four different countries.

I knew when I met Alan and Vincent that I had found researchers who had the same mindset and goals as me.

In late 1996 we discussed doing brain autopsies on actual patients. It was a patient in our LDSG that led us to our our first candidate. This patient was from a very endemic area of Wisconsin, and he too was all about finding answers through better science.

Jim’s father was a lifelong farmer, hunter and outdoorsman. Unfortunately this vibrant active man was now wasting away in a nursing home, he had dementia later confirmed by autopsy and the presence of amyloid plaques as Alzheimer’s disease. In addition to dementia this patient also had about a dozen symptoms of Lyme disease. More importantly he had two sons with Lyme disease that had been misdiagnosed with rheumatoid arthritis and MS who both recovered on long-term antibiotics (two years). The brothers both recovered on antibiotics and were now asking if their dying father could also have Lyme disease? And more to the point: did Lyme disease cause his dementia?

Jim Forris from Ashland WI battled with his family to do this autopsy. Like most families they just wanted this dark chapter in their lives to be closed and doing an autopsy was a lot of work, it was expensive, the process seemed morbid, and what guarantee was there that he would have spirochetes in his failing brain?

But Jim had the power of attorney over his father’s affairs, and without any more consultation he had his father’s brain harvested at death, and then shipped it to New York to Dr. Alan MacDonald.

The results were beyond our expectations. Jim’s father had Borrelia burgdorferi in every cross section of his brain. More importantly in 1997 Dr. MacDonald was the first to capture Borrelia intracellular inside neurons and had serial sections showing the spirochete could transit brain cells with apparent ease. Spirochetes were found attached to glial cells and many were seen in extracellular spaces.

Unfortunately at this time it was not even a consideration to stain for amyloid and Borrelia on the same slide. Alan would do this a decade later with spectacular results!

In medicine this should have been a huge deal.A major discovery. But inexplicably it was completely ignored. We even kept the stored unstained paraffin blocks available to the patient’s doctors and others to see for them selves. No one was willing to test the tissues for themselves.

When Jim approached his father’s doctors with the offer to share the formalin fixed brain with them for their own research, their response to Jim Forris’s sincere and generous offer was to get a restraining order. A restraining order! This was no longer just denial or ignorance, this was now obfuscation and obstruction of medical science. In medicine not only can ignorance be bliss, but it can also be used as plausible deniability.

Once it was determined that this dementia patient actually had Lyme disease and they had repeatedly denied even testing for Lyme: The response was that the clinic in Duluth MN wanted nothing more to do with this case or the family of the patient. All discussions were squashed!

These images below should have been regarded as a medical breakthrough just as important as finding the cause of Legionaire’s disease or the true cause of ulcers by H. pylori. Instead like all great finds in Lyme disease research, it was either ignored or met with disdain.

Intracellular Borrelia inside brain neurons and glial cells explained a lot about what we had been seeing in patients.

• Neuro Lyme patients often had severe neurologic symptoms
• Few bacteria were ever seen in the blood
• Blood tests were often negative due to low infection load in blood
• Patients often relapsed after recommended lengths of antibiotics
• Treatments required higher dose of antibiotics, that are dosed longer and often in combinations to reach therapeutic/bactericidal levels in the brain

We were excited at this finding, but had no idea of how much more convoluted the pathology would become. It became clear we had to better understand the interactions of Borrelia with brain cells.

We were elated when in 2006 the CDC funded study by doctors Jill Livengoode and Dr. Robert Gilmore. They confirmed our finding of Borrelia having the ability to penetrate both glial cells and human neurons. But inexplicably the very study that the CDC funded was almost immediately suppressed by the CDC, and several administrators even disparaged their work as though to contradict their findings by saying: “…this was a test tube study and means nothing.”

Neither Gilmore or Livengoode appear to be speaking openly about their collaboration? And to my knowledge do not publically make comments about its importance. A similar situation appears to be happening in Canada where researchers have photographed live Borrelia swimming through blood vessels with ease. What is going on?
What is the ultimate agenda with these denialists? It certainly isn’t science or they would fund a multi-national brain autopsy study to deny or confirm Alan’s and Livengoode’s work on intracellular penetration in-vivo.

Microbes Infect. 2006 Nov-Dec;8(14-15):2832-40. Epub 2006 Sep 22.

Invasion of human neuronal and glial cells by an infectious strain of Borrelia burgdorferi.

Livengood JA, Gilmore RD Jr.
Centers for Disease Control and Prevention, Division of Vector-borne Infectious Diseases, 3150 Rampart Road, CSU Foothills Campus, Fort Collins, CO 80522, USA.

So now with the CDC all but denying the existence of Livengoode and Gilmore’s work things looked even more bleak in the world of lyme disease pathology research.

=========================================

Enter Dr. Judith Mikklossy

Where my quest led me was to attend every science based Lyme conference that Tom Forschner and Karen Forschner of the LDF planned and administrated. (I believe the Lyme Disease Foundation conferences were for over a decade the most medically sound, research based Lyme conferences I ever attended.)

It was in 1997 when I first met Dr. Judith Miklossy a Neuro-Pathologist who had been researching dementia for several years. Judith presented her Swiss study of brain-autopsies on 13 Alzheimer’s patients. All 13 had spirochetes and her aged matched controls (no dementia) were negative for Borrelia.

Judith even isolated live bacteria from one of the subjects. This would lead to several more studies including using that isolate to measure the effects on rat-brain cultures. Dr. Mikklossy continues to focus on Borrelia and its role in causing dementia, and its prevalence in Alzheimer’s brains.

https://jneuroinflammation.biomedcentral.com/…/1742-2094-8-…

But there was another pathologist presenting at the same conference and he also had been working with the idea that Borrelia was playing a role on the pathology of Alzheimer’s Dementia. His name was Dr. Alan MacDonald MD, and he had a keen interest in not only the spiral form, but also the spherical forms of Borrelia, and felt they had a role in the pathogenesis of dementia.

MacDonald AB: Borrelia in the brains of patients dying with dementia. JAMA. 1986, 256: 2195-2196.

While Judith was concentrating on the mechanism of pathogenesis by looking at Rat-Brain model, Alan’s method was to work backwards: Alan chose to look at hundreds of brain sections from hundreds of Alzheimer’s patients, and to look at what the end process of neuroborreliosis looks like, and to attempt to explain the mecahnisms of changes seen in the Alzheimer’s brain.

When we combine Mikklossy’s work and Alan MacDonald’s work, we see that they meet in the middle reaching similar conclusions and findings.

McGeer PL, Itagaki S, Tago H, McGeer EG: Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci Lett. 1987, 79: 195-200. 10.1016/0304-3940(87)90696-3.

Mikklossy

Dr. Judith Mikklossy investigated how Borrelia interacts with specific brain cells, and developed what for all intents is a petri dish model of Alzheimer’s disease. All the markers we look to see in Alzheimer’s brain is found withing mere weeks of adding Borrelia burgdorferi to rat brain cultures.

With the addition and enrichment with brain-microglia cells, the various cells immediately produced its first marker: precursor amyloid protein.

These are the other markers she observed in just eight weeks.

1 Precursor Amyloid Protein APP production
2 Cleavage of APP to Beta Amyloid
3 Conversion to Beta sheet amyloid
4 Hyperphosphoralation of microtubule protein Tau
5 Neurofibrillary tangles
6 Vacuole-like spaces

Everything we expect to see in an Alzheimer’s brain was seen except true plaques.

MacDonald

Alan took a different approach to Alzheimer’s research and the role of spirochetes.

Registering more living patients for brain autopsies is an extremely slow process with poor success rate because family members will often go against the patient’s wishes and at the last minute will cancel the tissue harvest. Also the process is expensive without an institution with the equipment and funding to do the work.

Here is what is involved with registering patients for a brain autopsy:

• A family discussion and agreement to pursue pathology research
• Legal consent forms must be signed
• Costs per brain are $1,000-5,000 depending on what is done
• A large enough patient sample across many states is needed to be statistically relevant.
• Expert techniques are needed in: sectioning, staining, and fluorescent microscopy using individually designed DNA probes
• Storage of samples
• Data analysis

As a way to speed up the process and reduce costs and legal concerns, Alan ordered brain samples (both frozen and paraffin blocks) from Alzheimer’s Brain Banks like Harvard.

Alan sectioned and stained hundreds of samples and found some amazing things that I have listed below.

• Borrelia often forms biofilms within the human Alzheimer’s brain
• More than one species of Borrelia is involved
• The spirochetes either attract amyloid or helps produce it as the bacteria biofilms are found interspersed inside the amyloid plaques
• Nematode worms are sometimes seen in the diseased brain of both MS and Alzheimer’s patients
• The nematode gut stains positive by DNA probes for Borrelia
• The nematodes destroy brain tissue and deposits feces and eggs in the brain
• Borrelia biofilms are seen in fatal glioblastoma tumors
• Both Borrelia burgdorferi and Borrelia mayonii have been found within the testicle of one patient
• In severe dementia, amyloid can sometimes be detected in the blood using amyloid stains, this might be a blood test for Alzheimer’s?

So while Dr Mikklossy looks for the genesis of Alzheimer’s disease, Alan MacDonald looks at the end state of the disease process and asks what the role Borrelia play?

They have reached similar conclusions:

• Borrelia can form “colonies or biofilms” in the brain.
• Borrelia can penetrate blood vessels and weaken blood vessels possibly leading to strokes
• Borrelia bacteria have a tropism (attraction) for the brain and for specific brain cells.
• Borrelia is found both intracellular and extracellular in the brain
• While the bacteria is detected in the brain by autopsy, the blood can remain negative for the associated antibodies
• The blood-brain-barrier represents a therapeutic challenge to treat effectively and maybe considered a treatable but incurable condition
• Borrelia may well be part of the biochemical process that leads to amyloid production
• The debate over whether Borrelia like Syphilis can cause dementia is now overwhelmingly supportive of a new category of dementia: “Borrelia Associated Dementia”

END PART ONE

https://jneuroinflammation.biomedcentral.com/…/1742-2094-8-…

MacDonald AB: Borrelia in the brains of patients dying with dementia. JAMA. 1986, 256: 2195-2196.

MacDonald AB, Miranda JM: Concurrent neocortical borreliosis and Alzheimer’s disease. Hum Pathol. 1987, 18: 759-761. 10.1016/S0046-8177(87)80252-6
MacDonald AB: Concurrent neocortical borreliosis and Alzheimer’s Disease. Ann N Y Acad Sci. 1988, 539: 468-470. 10.1111/j.1749-6632.1988.tb31909.x.
Pappolla MA, Omar R, Saran B, Andorn A, Suarez M, Pavia C, Weinstein A, Shank D, Davis K, Burgdorfer W: Concurrent neuroborreliosis and Alzheimer’s disease: analysis of the evidence. Hum Pathol. 1989, 20: 753-757. 10.1016/0046-8177(89)90068-3.

Miklossy J, Kuntzer T, Bogousslavsky J, Regli F, Janzer RC: Meningovascular form of neuroborreliosis: similarities between neuropathological findings in a case of Lyme disease and those occurring in tertiary neurosyphilis. Acta Neuropathol. 1990, 80: 568-572. 10.1007/BF00294622.

Miklossy J: Alzheimer’s disease – A spirochetosis?. Neuroreport. 1993, 4: 841-848. 10.1097/00001756-199307000-00002.

Baker HF, Ridley RM, Duchen LW, Crow TJ, Bruton CJ: Evidence for the experimental transmission of cerebral beta-amyloidosis to primates. Int J Exp Pathol. 1993, 74: 441-454.

Baker HF, Ridley RM, Duchen LW, Crow TJ, Bruton CJ: Experimental induction of beta-amyloid plaques and cerebral angiopathy in primates. Ann N Y Acad Sci. 1993, 695: 228-231. 10.1111/j.1749-6632.1993.tb23057.x.

Baker HF, Ridley RM, Duchen LW, Crow TJ, Bruton CJ: Induction of beta (A4)-amyloid in primates by injection of Alzheimer’s disease brain homogenate. Comparison with transmission of spongiform encephalopathy. Mol Neurobiol. 1994, 8: 25-39. 10.1007/BF02778005.

MacDonald, Alan in European Journal of Clinical Microbiology 32(8) · March 2013 with 32 Reads

Alzheimer’s disease Braak Stage progressions: Reexamined and redefined as Borrelia infection transmission through neural circuits Medical Hypotheses 68(5):1059-64 · February 2007
Alzheimer’s neuroborreliosis with trans-synaptic spread of infection and neurofibrillary tangles derived from intraneuronal spirochete in Medical Hypotheses 68(4):822-5 · February 2007 with
MacDonald, Alan Alzheimer’s & dementia: the journal of the Alzheimer’s Association 2(3) · July 2006

Spirochetal cyst forms in neurodegenerative disorders,… hiding in plain sightArticle in Medical Hypotheses 67(4):819-32 · February 2006
Gestational Lyme borreliosis. Implications for the fetusArticle · Literature Review in Rheumatic Disease Clinics of North America15(4):657-77 · December 1989
Miklossy J, Kasas S, Janzer RC, Ardizzoni F, Van der Loos H: Further morphological evidence for a spirochetal etiology of Alzheimer’s Disease. NeuroReport. 1994, 5: 1201-1204.
Schaeffer S, Le Doze F, De la Sayette V, Bertran F, Viader F: Dementia in Lyme disease. Presse Med. 1994, 123: 861
Fallon BA, Nields JA: Lyme disease: a neuropsychiatric illness. Am J Psychiatry. 1994, 151: 1571-1583.
Miklossy J: The spirochetal etiology of Alzheimer’s disease: A putative therapeutic approach. Alzheimer Disease: Therapeutic Strategies. Proceedings of the Third International Springfield Alzheimer Symposium. Edited by: Giacobini E, Becker R. 1994, Birkhauser Boston Inc., 41-48. Part I
Miklossy J, Gern L, Darekar P, Janzer RC, Van der, Loos H: Senile plaques, neurofibrillary tangles and neuropil threads contain DNA?. J Spirochetal and Tick-borne Dis (JSTD). 1995, 2: 1-5.
Miklossy J, Darekar P, Gern L, Janzer RC, Bosman FT: Bacterial peptidoglycan in neuritic plaques in Alzheimer’s disease. Azheimer’s Res. 1996, 2: 95-100.
Miklossy J: Chronic inflammation and amyloidogenesis in Alzheimer’s disease: Putative role of bacterial peptidoglycan, a potent inflammatory and amyloidogenic factor. Alzheimer’s Rev. 1998, 3: 45-51.
Miklossy J, Khalili K, Gern L, Ericson RL, Darekar P, Bolle L, Hurlimann J, Paster BJ: Borrelia burgdorferi persists in the brain in chronic Lyme neuroborreliosis and may be associated with Alzheimer disease. J Alzheimer’s Dis. 2004, 6: 1-11.
Miklossy J, Kis A, Radenovic A, Miller L, Forro L, Martins R, Reiss K, Darbinian N, Darekar P, Mihaly L, Khalili K: Beta-amyloid deposition and Alzheimer’s type changes induced by Borrelia spirochetes. Neurobiol Aging. 2006, 27: 228-236. 10.1016/j.neurobiolaging.2005.01.018.

Miller LM, Wang Q, Telivala TP, Smith RJ, Lanzirotti A, Miklossy J: Synchrotron-based infrared and X-ray imaging shows focalized accumulation of Cu and Zn co-localized with beta-amyloid deposits in Alzheimer’s disease. J Struct Biol. 2006, 155: 30-37. 10.1016/j.jsb.2005.09.004.

MacDonald AB: Plaques of Alzheimer’s disease originate from cysts of Borrelia burgdorferi, the Lyme disease spirochete. Med Hypotheses. 2006, 67: 592-600. 10.1016/j.mehy.2006.02.035.

Larsen P, Nielsen JL, Dueholm MS, Wetzel R, Otzen D, Nielsen PH: Amyloid adhesins are abundant in natural biofilms. Environ Microbiol. 2007, 9: 3077-3090. 10.1111/j.1462-2920.2007.01418.x.

Meer-Scherrer L, Chang Loa C, Adelson ME, Mordechai E, Lobrinus JA, Fallon BA, Tilton RC: Lyme disease associated with Alzheimer’s disease. Curr Microbiol. 2006, 52: 330-332. 10.1007/s00284-005-0454-7.
Miklossy J: Chronic inflammation and amyloidogenesis in Alzheimer’s disease – role of spirochetes. J Alzheimer’s Dis. 2008, 13: 381-391.

Honjo K, van Reekum R, Verhoeff NP: Alzheimer’s disease and infection: do infectious agents contribute to progression of Alzheimer’s disease?. Alzheimers Dement. 2009, 5: 348-360. 10.1016/j.jalz.2008.12.001.
Loeb MB, Molloy DW, Smieja M, Standish T, Goldsmith CH, Mahony J, Smith S, Borrie M, Decoteau E, Davidson W, McDougall A, Gnarpe J, O’DONNell M, Chernesky M: A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer’s disease. J Am Geriatr Soc. 2004, 52: 381-387. 10.1111/j.1532-5415.2004.52109.x.PubMedGoogle Scholar
Tsai GE, Falk WE, Gunther J, Coyle JT: Improved cognition in Alzheimer’s disease with short-term D-cycloserine treatment. Am J Psychiatry. 1999, 156: 467-469.PubMedGoogle Scholar
Kim HS, Suh YH: Minocycline and neurodegenerative diseases. Behav Brain Res. 2009, 196: 168-179. 10.1016/j.bbr.2008.09.040.
Miklossy J, Kasas S, Zurn AD, McCall S, Yu S, McGeer PL: Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis. J Neuroinflammation. 2008, 5: 40-10.1186/1742-2094-5-40.

McGeer PL, McGeer EG: Local neuroinflammation and the progression of Alzheimer’s disease. J Neurovirol. 2002, 8: 529-538. 10.1080/13550280290100969.

Guo JP, Arai T, Miklossy J, McGeer PL: Abeta and tau form soluble complexes that may promote self aggregation of both into the insoluble forms observed in Alzheimer disease. Proc Natl Acad Sci USA. 2006, 103: 1953-1938. 10.1073/pnas.0509386103.

Miklossy J, Rosemberg S, McGeer PL: Beta amyloid deposition in the atrophic form of general paresis. Alzheimer’s Disease: New advances. Proceedings of the 10th International Congress on Alzheimer’s Disease (ICAD). Edited by: Iqbal K, Winblad B, Avila J. 2006, Medimond, International Proceedings, 429-433.

Miklossy J: Biology and neuropathology of dementia in syphilis and Lyme disease. Dementias. Edited by: Duyckaerts C, Litvan I. 2008, Edinburgh, London, New York, Oxford, Philadelphia, St-Louis, Toronto, Sydney: Elsevier, 825-844. Series Editor Aminoff MJ, Boller F, Schwab DS: Handbook of Clinical Neurology vol. 89