13 August 2014
I am writing this letter in reference to the recent paper by Danton and Catalano . I have read with interest their investigation based on the anticipation that “If the biological agent Borrelia burgdorferi that causes LD (Lyme disease) also causes AD (Alzheimer’s disease), then areas with the highest levels of LD should have significantly higher numbers of deaths due to AD compared to low LD areas.”
To compare AD populations suffering from Lyme neuroborreliosis in endemic and non-endemic areas would be the right approach to obtain an answer to the question raised by the authors.
From 1993 it was emphasized, that Borrelia burgdorferi alone cannot explain all AD cases, as the incidence of Lyme disease, and particularly of Lyme dementia, compared to AD is very low. The authors noticed that various types of spirochetes were suggested to play a role in AD and to consider this point in their investigation would be critical [2,3]. These various spirochetes, including the highly prevalent periodontal pathogen Treponemes were detected in more than 90% of AD cases [4,5]. It is therefore expected that in both endemic and non-endemic LD areas, AD caused by other spirochetes can strongly overlap the small proportion of AD cases caused by Borrelia burgdorferi alone. Consequently, the present study cannot prove or exclude the involvement of Borrelia burgdorferi in AD.
It is also important to consider that only about 10-15% of Lyme patients and generally only those who are untreated or insufficiently treated will develop dementia caused by Borrelia burgdorferi. Therefore, to simply compare the incidence of Lyme disease with that of AD may further render the interpretation of the results difficult.
The authors also state that “The relationship between LD and AD has also been supported by analysis of existing data using Koch’s and Hill’s Postulates . What is lacking to fulfill these postulates is the isolation of functional entities (e.g., B. burgdorferi) followed by proof of their ability to induce AD-related events in tissue culture cells.”
The isolation of spirochetes from AD brains [1,6,7] and exposure of mammalian primary cell and organotypic cultures to spirochetes were shown to reproduce lesions similar to the pathological and biological hallmarks of AD . The re-isolation of spirochetes (Borrelia burgdorferi) from cell cultures infected by B31 reference strain and those cultivated from AD brains, all induced lesions similar to AD, they revealed to be virulent, invaded neurons and glial cells, and caused nuclear fragmentation, which were all previously documented . But independently of these observations, it is noteworthy that Koch himself acknowledged that the application of his four postulates to establish causality should be used as guidelines and not as definite postulates . Indeed, like Treponema pallidum, several other bacteria and viruses cannot be grown in pure culture and consequently cannot be re-isolated. Despite of this, the causal relationship between Treponema pallidum and syphilitic dementia is established. In order to address the limitations of Koch’s postulates, Hill introduced his new criteria for causality . Hill’s nine postulates do not require the isolation of the microorganisms in pure culture or their re-isolation from infected cell cultures.
This letter is guided with the best intention to openly discuss this newly emerging field of AD research in order not to stop but to help and encourage further investigations in this direction. An infectious etiology of AD was first proposed a century ago and it was never discarded. Leading AD researchers [12,13] about three decades ago claimed that an infectious etiology of AD is a real possibility and cannot be disregarded. To further consider the involvement of various types of spirochetes and co-infections with various bacteria, including Chlamydia pneumoniae , Porphyromonas gingivalis , and various viruses, like herpes simplex virus type 1 (HSV-1) , in AD is critical, particularly as these microorganisms were also detected in various other chronic inflammatory disorders, which are associated with AD.
We do not possess a targeted therapy for AD. If AD is caused by spirochetal infection associated with other bacteria and viruses, this might bring new hope for all patients who are suffering from AD and for all those who have concerns about the relationship between LD, periodontal pathogen spirochetes, and AD, as syphilitic dementia was almost eradicated by the use of penicillin. As we have an example in the history of medicine that chronic spirochetal infection can cause dementia and reproduce the pathological hallmarks of AD, including amyloid-β deposition , prompt action is needed to promote this research not only by the neuroscience community but also by governmental health authorities as AD might be prevented.
Judith Miklossy, Director, Prevention Alzheimer International Foundation, International Alzheimer Research Center, Martigny-Croix, Switzerland
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