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"A scientist who is also a human being cannot rest, while knowledge, which might reduce suffering rests on the shelf”

Dr Albert B. Sabin, developer of the oral polio vaccine; http://sabin. [Found and taken from the web-cite of a colleague. Thanks]


PREVENTION ALZHEIMER INTERNATIONAL FOUNDATION

www.preventionalzheimer.org

THE GOAL OF THIS INTERNATIONAL FOUNDATION IS TO HELP RESEARCH WITHOUT  FRONTIERS FOR THE PREVENTION OF ALZHEIMER'S DISEASE AND HELP RESEARCH ON CHRONIC/LATE LYME DISEASE

DR Judith Miklossy who is the Director of this international foundation and research center is one of the pioneers in this domain of research.

IT IS ONLY TOGETHER, WITH  HELP OF THE SOCIETY, PRIVATE ORGANOSATIONS, GOVERNEMENTS AND INDIVIDUAL DONATIONS THAT WE CAN GO FASTER AHEAD.

PREVENTION ALZHEIMER FOUNDATION
An international foundation registered in Switzerland
www.preventionalzheimer.org                                                                                                                                Director: Judith Miklossy MD, PhD, DsC
Address: 1921 Martigny-Croix, CP 16, 1921, Switzerland
Tel: + 41 27 722 0652; Cell: + 41 79 207 4442
Would you like to participate and help with donation?

Bank account of the foundation:
Banque Cantonale du Valais
Rue des Cèdres 8, Sion
1950, Switzerland
IBAN: CH71 0076 5001 0105 7880 3
Account number: 101 057 8803 
BIC ou SWIFT: BCVSCH2L
Clearing number or CB: 765

Actualities from June to December 2012

CHRONIC OR LATE LYME DISEASE

 In the framework of an international effort, a special issue with the participation of internationally recognized experts critically and constructively overviewed the clinical and pathological aspects of Lyme neuroborreliosis and showed directions for future practice and research


Editorial: Judith Miklossy, Samuel Donta, Kurt Mueller, Oliver Nolte and George Perry   Chronic or Late Lyme Neuroborreliosis: Present and Future The Open Neurology Journal, 2012, 6, (S 1-M1) 78 http://www.benthamscience.com/open/toneuj/articles/V006/SI0078TONEUJ/78TONEUJ.pdf 

Abstract

This special issue gives a framework of an international effort, to critically and constructively overview the clinical and pathological aspects of Lyme neuroborreliosis and show directions for future practice and research. Borrelia burgdorferi in association with tertiary brain lesions were reported by many authors. These observations indicate that similarly to Tre-ponema pallidum, Borrelia burgdorferi infection is directly involved in the late or chronic manifestations of Lyme neuroborreliosis. Chronic or late Lyme neuroborreliosis both refer to tertiary neuroborreliosis, therefore, the use of these terms as different entities is not justified and may lead to confusion.

The issue in the diagnosis and treatment of Lyme neuro-orreliosis is assessed followed by a comprehensive analysis of the involvement of connective tissue and associated clini-cal manifestations. A critical review shows that both the meningovascular and meningoencephalitic forms, which define chronic or late neurosyphilis also occur in Lyme neuroborreliosis. Clinical and pathological confir-mation of these tertiary forms and detection of

A critical assessment of clinical trials will guide the de-sign of future clinical studies and a detailed analysis of vari-ous factors influencing PCR detection of Borrelia specific DNA would be precious to improve the sensitivity of this  potentially important diagnostic tool. 

An update on the virulence determinants of Borrelia burgdorferi and the pathomechanisms involved in Lyme disease is discussed followed by a review showing the im-portance of co-infections in the diagnosis and treatment of Lyme disease.

Evidence for an infectious origin of various neuro-psychiatric symptoms of tick-borne diseases and various psychiatric disorders are also discussed. The involvement of immune system reactions, chronic inflammation, genetic and environmental factors are also considered. Finally an update on the perspectives on Lyme Borreliosis in Canada closes the special issue.

The majority of authors are internationally recognized neurologists and scientists with extensive experience and complementary expertise in clinical and/or basic research on Lyme disease. The exchange of knowledge at an interna-tional level and between experts in various branches of medicine and in basic research is the way to advance faster in this new, promising and important field of medicine. The aim of this special issue is to contribute to this process. This approach motivated the authors at the annual meeting of the German Borreliosis Society (Deutsche Borreliose-Gesells-chaft, DBG) in 2011 at Wuppertal, Germany to initiate and realize this special issue.

This issue is dedicated to the memory of Mark A. Smith whose untimely death has left a void for those looking to novel ideas to solve chronic diseases.


June 2012

Judith Miklossy Chronic or Late Lyme Neuroborreliosis: Analysis of Evidence Compared
to Chronic or Late Neurosyphilis The Open Neurology Journal, 2012, 6, 146-157 
http://www.benthamscience.com/open/toneuj/articles/V006/SI0078TONEUJ/146TONEUJ.pdf

Abstract

Whether spirochetes persist in affected host tissues and cause the late/chronic manifestations of neurosyphilis was the subject of long-lasting debate. Detection of a direct link between persisting infection and tertiary manifestations of neurosyphilis.Treponema pallidum in the brains of patients with general paresis established a link between persisting infection and tertiary manifestations of neurosyphilis.

Today, the same question is in the center of debate with respect to Lyme disease. The goal of this review was to compare the established pathological features of neurosyphilis with those available for Lyme neuroborreliosis. If the main tertiary forms of neurosyphilis also occur in Lyme neuroborreliosis and would indicate that the spirochete is responsible for the neuropsychiatric manifestations of late/chronic Lyme neuroborreliosis.

The substantial amounts of data available in the literature show that the major forms of late/chronic Lyme neuroborreliosis (meningovascular and meningoencephalitis) are clinically and pathologically confirmed. Borrelia burgdorferi was detected in association with tertiary brain lesions and cultivated from the affected brain or cerebrospinal fluid. The accumulated data also indicate that Borrelia burgdorferi is able to evade from destruction by the host immune reactions, persist in host tissues and sustain chronic infection and inflammation. These observations represent evidences that Borrelia burgdorfei in an analogous way to Treponema pallidum is responsible for the chronic/late manifestations of Lyme neuroborreliosis.

Late Lyme neuroborreliosis is accepted by all existing guidelines in Europe, US and Canada. The terms chronic and late are synonymous and both define tertiary neurosyphilis or tertiary Lyme neuroborreliosis. The use of chronic and late Lyme neuroborreliosis as different entities is inaccurate and can be confusing. Further pathological investigations and the detection of spirochetes in infected tissues and body fluids are strongly needed.


August - September 2011

Increasing amount of data indicate that spirochetes are involved in the pathogenesis of Alzheimer's disease. Here we review historic and new data related to the involvement of spirochetes in Alzheimer's disease. All positive and negative data are included. The goal was to critically analyze the association and causality between spirochetes and Alzheimer's disease, based on the substantial amount of data available and on established objective criteria of Koch and Hill

F1000 evaluation: "An infectious origin of Alzheimer'sdisease has been suggested for many decades. In a wonderfully synthetic review, a convincing role for neurospirochetesis made. This review opens a new perspective on the pathogenesis of Alzheimer's and other neurodegenerative diseases."

Miklossy J. Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria. J Neuroinflammation. 2011 Aug 4;8:90

 Abstract

It is established that chronic spirochetal infection can cause slowly progressive dementia, brain atrophy and amyloid deposition in late neurosyphilis. Recently it has been suggested that various types of spirochetes, in an analogous way to Treponema pallidum, could cause dementia and may be involved in the pathogenesis of Alzheimer’s disease (AD). Here, we review all data available in the literature on the detection of spirochetes in AD and critically analyze the association and causal relationship between spirochetes and AD following established criteria of Koch and Hill. The results show a statistically significant association between spirochetes and AD (P = 1.5 x 10-17, OR = 20, 95% CI = 8-60, N = 247).
When neutral techniques recognizing all types of spirochetes were used, or the highly prevalent periodontal pathogen Treponemas were analyzed, spirochetes were observed in the brain in more than 90% of AD cases. Borrelia burgdorferi was detected in the brain in 25.3% of AD cases analyzed and was 13 times more frequent in AD compared to controls. Periodontal pathogen Treponemas (T. pectinovorum, T. amylovorum, T. lecithinolyticum, T. maltophilum, T. medium, T. socranskii) and Borrelia burgdorferi were detected using species specific PCR and antibodies. Importantly, co-infection with several spirochetes occurs in AD. The pathological and biological hallmarks of AD were reproduced in vitro. The analysis of reviewed data following Koch’s and Hill’s postulates shows a probable causal relationship between neurospirochetosis and AD. Persisting inflammation and amyloid deposition initiated and sustained by chronic spirochetal infection form together with the various hypotheses suggested to play a role in the pathogenesis of AD a comprehensive entity.As suggested by Hill, once the probability of a causal relationship is established prompt action is needed. Support and attention should be given to this field of AD research. Spirochetal infection occurs years or decades before the manifestation of dementia. As adequate antibiotic and anti-inflammatory therapies are available, as in syphilis, one might prevent and eradicate dementia.

                                          _______________________________

Miklossy J. Emerging roles of pathogens in Alzheimer disease. Expert Reviews of  Molecular Medicine 2011 ; 13: e30.

In this review all pathogens (bacteria and viruses) were considered. All positive and negative data were included. In addition to the critical review of available data, the molecular mechanisms involved in chronic slowly progressive infectious dementia and suggestions for future investigations are included.

Abstract

Chronic spirochetal infection can cause slowly progressive dementia, cortical
atrophy and amyloid deposition in the atrophic form of general paresis. There
is a statistically significant association between various types of spirochete
(including the periodontal pathogens Treponemas and Borrelia burgdorferi),
Chlamydophyla pneumoniae, herpes simplex virus type-1 (HSV-1) IgM levels
and Alzheimer disease (AD). Although there is no significant difference
between the frequency of HSV-1 in AD cases and age-matched controls, the
number of ApoE4 HSV-1 carriers with AD is reported to be significantly higher
compared with disease occurrence in noncarriers. Exposure of mammalian
neuronal and glial cells and organotypic cultures to spirochetes reproduces
the biological and pathological hallmarks of AD. Senile-plaque-like beta
amyloid (Aβ) deposits are also observed in mice following inhalation of
C. pneumoniae in vivo, and Aβ accumulation and phosphorylation of tau is
induced in neurons by HSV-1 in vitro and in vivo. Specific bacterial ligands, and
bacterial and viral DNA and RNA all increase the expression of
proinflammatory molecules, and activate the innate and adaptive immune
systems. Evasion of pathogens from destruction by the host immune reactions
leads to persistent infection, chronic inflammation, neuronal destruction and
Aβ deposition. Aβ has been shown to be a pore-forming antimicrobial peptide,
indicating that Aβ accumulation might be a response to infection. Global
attention and action is needed to support this emerging field of research
because dementia might be prevented by combined antibiotic/antiviral and
anti-inflammatory therapy.


May 2010

Amyloid beta, which is the most important biological marker of Alzheimer's disease, revealed to be an anttimicrobial peptide (AMP) following an excellent team work between several Universities such as Mass. General Institute for Neurodegenerative Disease and Dept. of Neurology,  Boston University School of Medicine, Beth Israel Deaconess Medical Center, Uppsala University, Uppsala, Sweden and Boston University, Boston, MA.

Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD. The Alzheimer's Disease-Associated Amyloid beta-Protein Is an Antimicrobial Peptide. PLoS One. 2010 Mar 3;5(3):e9505


September 2008 Diabetes type 2 - similarities to Alzheimer's disease

There is a strong association between Alzheimer's disease and type 2 diabetes.  Recent observations show a seroprevalance of various infectious agents in type 2 diabetes. The association of periodontal disorders, which are polybacterial disorders, with Alzheimer's disease and type 2 diabetes suggests that infection and local inflammation can play an important role in these chronic age related disorders.

The following manuscript shows for the first time that d various chronic bacterial infections and local inflammation can play an important role in type 2 diabetes. Chlamydia pneumoniae, Helicobacter pylorii and spirochetes (probably, as in Alzheimer's disease, various types of spirochetes,  including periodontal and intestinal spirochetes ) are amoung the candidate pathogens. Antibiotics together with antiinflammatory drugs may slow down and prevent the disease. 

Miklossy J, Martins RN, Darbinian N, Khalili K, McGeer PL. Type 2 diabetes: Local inflammation and direct effect of bacterial toxic products. Open Pathol J, 2008, 2: 86-95.

http://www.bentham-open.org/pages/content.php?TOPATJ/2008/00000002/00000001/86TOPATJ.SGM

 Abstract:

It has been known for almost a century that amyloidosis is frequently associated with chronic bacterial infection. Islet amyloid deposit is characteristic of type 2 diabetes.  Periodontal disease, which is predominantly caused by several Gram negative bacteria, is a risk factor for type 2 diabetes. The goal of the study was to explore whether bacteria or their toxic components may play a role in type 2 diabetes. The pancreas in 22 autopsy cases were analyzed for the presence of lipopolysaccharide (LPS), bacterial peptidoglycan (BPG) and local inflammatory processes. Ten of the cases had clinically diagnosed type 2 diabetes, and 12 were age matched controls.  The results of an immunohistochemical analysis showed the presence of LPS and BPG in association with islet amyloid deposits in all the 10 diabetic cases as well as in 3 controls with clinically silent amyloid deposits. Chlamydia pneumoniae and Helicobacter pylori specific antigens were detected in the affected islets in a subset of diabetic patients. Clumps of HLA-DR positive activated macrophages, abundant immunoreactivity to the activated complement components C3d, C4d and C5b-9, the terminal attack complex, and a moderate numbers of T4 and particularly of T8 lymphocytes were present in the pancreas of all diabetic cases.  These results suggest that bacteria or their slowly degradable remnants may initiate and sustain chronic inflammation in the pancreas and therefore play a role in the pathogenesis of type 2 diabetes. They also indicate that local immune responses, including activation of the classical complement pathway are important in the pathogenesis of type 2 diabetes. There may also be some involvement of the adaptive immune system. Further investigations are essential since a parallel use of antibacterial and antiinflammatory drugs may prevent or slow down the disease progression.


September 2008

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
 Journal of Neuroinflammation, 2008; 5: 40 (open access, highly accessed)

http://www.jneuroinflammation.com/content/5/1/40

This work shows the presence and persistence of atypical pleomorphic and cystic forms of Borrelia burgdorferi in the brains of three patients with neuropathologically and serologically confirmed Lyme neuroborreliosis. Borrelia burgdorferi was also cultivated from the brains of these patients. The in vivo observed pleomorphic forms of Borrelia spirochetes were identical to those induced in vitro.

The persistence of these more resistant spirochete forms and their intracellular location in host cells, (neurons and glial cells) may be one of those factors, which are responsible for the long latent stage of the disease and the persistence of Borrelia infection. The results also indicate that Borrelia burgdorferi can induce cellular dysfunction and apoptosis.

The abundant HLA-DR activated microglia and reactive astrocytes in the infected brain are indicative of Borrelia induced chronic local inflammation. The detection and recognition of atypical, cystic and granular forms of Borrelia burgdorferi in infected tissues is essential for the diagnosis and the treatment of Lyme disease as they can occur in the absence of typical spiral Borrelia form.

These results suggest that in such cases an adequate and more prolonged antibiotic therapy may be necessary.


ALZHEIMER DISEASE - THE ATROPHIC FORM OF LATE  NEUROSPIROCHETOSES

THE INVOLVEMENT OF SEVERAL TYPES OF SPIROCHETES SHOULD BE CONSIDERED AND ANALYZED IN ALZHEIMER'S DISEASE! BORRELIA BURGDORFERI IS ONLY ONE OF THEM. PERIODONTAL ORAL TREPONEMA SPIROCHETES ARE HIGHLY PREVALENT IN THE POPULATION AT LARGE AND MAY BE FREQUENT CANDIDATES IN ALZHEIMER'S DISEASE. INTESTINAL SPIROCHETES AND SPIROCHETES OF THE UROGENITAL TRACTS AND VARIOUS OTHER BORRELIA SPIROCHETES  MAY ALL BE INVOLVED IN ALZHEIMER DISEASE. THEREFORE STUDIES CONSIDERING AND ANALYZING BORRELIA BURGDORFERI  ALONE CAN BE DISAPPOINTING. SUCH STUDIES CANNOT EXCLUDE OR REINFORCE THE INVOLVEMENT OF BORRELIA BURGDORFERI IN ALZHEIMER'S DISEASE.

To analyze the involvement of Borrelia burgdorferi in Alzheimer patients who have a positive serology for Borrelia burgdorferi is essential. If we would like to analyze the involvement of Treponema pallidum in  a population with dementia without syphilis we would never succeed, despite that it has been known from a century that this spirochete can cause dementia.  

In those studies who failed to show the involvement of Borrelia burgdorferi in Alzheimer's disease, the Alzheimer's patients investigated had no positive serology for Borrelia burgdorferi indicating, these these patients did not suffer from Lyme disease. However in those studies where Borrelia burgdorferi was found to be implicated in Alzheimer's disease, Borrelia spirochetes were cultivated in BSK medium from the brains (MacDonald 1987, Miklossy, 1993, Miklossy 1994, 2004) and/or the patients showed a positive serology for Lyme disease (Miklossy et al., 2004; Miklossy, 2007 ) or a positive PCR for Borrelia burgdorferi (Riviere et al., 2004).

The goal of our initial studies was not to show the involvement of Borrelia burgdorferi alone in Alzheimer's disease but  to show that several types of spirochetes of the order Spirochaetales are involved in Alzheimer disease,  including Borrelia burgdorferi (Miklossy, 1993-1996, Miklossy et al 1994-2011). The title of the report clearly indicates: Alzheimer's disease - A spirochetosis? and not Alzheimer's disease - A neuroborreliosis? In addition, the hypothesis was based on the observation, that in the brain of a demented patient with atrophic general paresis - used as positive control for the detection of spirochetes - the silver technique for spirochetes revealed the pathology of Alzheimer's disease. At high magnification the regular spiral form and the atypical forms of Treponema pallidum clearly showed that the plaques are made up of Treponema spirochetes and correspond to spirochetal masses. Recently, the local cortical amyloid deposit in the atrophic form of  general paresis was characterized and, as in Alzheimer disease, corresponds to beta-amyloid.

Those who were analyzing all types of spirochetes including oral periodontal pathogen Treponemas, which are expected to be frequent candidates (Miklossy, 1993; Riviere et al, 2004) detected spirochetes in more than 90% of the Alzheimer's cases analyzed.

It is known that spirochetes frequently co-infect with other bacteria. Therefore, the consideration of co-infecting pathogens in Alzheimer's disease is also important.

The accumulated old historic and new observations and the fact that Fischer suggested (1907) and Alois Alzheimer and his colleagues cited Fischer's suggestion and stated that Fischer was not able to cultivate the microorgansisms. We should remember that Treponema pallidum cannot be cultivated and maintained in synthetic medium even today.


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