Herbert B Allen*, Diego Morales, Krister Jones and Suresh G Joshi
Drexel University College of Medicine, Philadelphia, USA
Received date: March 23, 2016; Accepted date: April 23, 2016; Published date: April 25, 2016
Citation: Allen HB, Morales D, Jones K, Joshi SG (2016) Alzheimers Disease: A Novel Hypothesis for the Development and the Subsequent Role of Beta Amyloid. J Neuroinfect Dis 7:211. doi:10.4172/2314-7326.1000211
Copyright: © 2016 Allen HB, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Spirochetes, biofilms, innate immune system activity have all been recently found in the brains of Alzheimer's disease patients. The mechanism and actions of those entities in producing the disease were postulated in those studies. The production and role of beta amyloid were not included in the discussion; we hypothesize herein how the development of that molecule occurs as a result of the Toll-like receptor 2 activation leading not only to TNFα, but also NFκB which themselves have been previously shown to induce the secretases necessary to cleave the amyloid precursor protein. This leads directly to beta amyloid. The beta amyloid (Aβ) has been shown to be antimicrobial, and its presence on and around the hippocampal plaques (the pathological hallmark of Alzheimer's disease) has been demonstrated. It becomes apparent that the Aβ tries to kill the spirochetes but cannot penetrate the biofilm. Its buildup then interrupts and destroys the neurocircuitry of the brains.
Spirochetes; Biofilm; Toll-like receptor 2; Secretases; TNFα; NFκB, Beta amyloid; Autoimmunity
We recently have demonstrated pathologically that biofilms are present in the brains of Alzheimer’s disease (AD) patients  (Figure 1). The biofilms were undoubtedly created by the dental and Lyme spirochetes which have previously been shown to be present there [2-5]; consequently, these biofilms would represent a chronic infection : We also provided immunopathological evidence that the innate immune system reactant, Toll-like receptor 2 (TLR 2), was upregulated in that same tissue (Figure 2). We postulated that TLR 2, while trying to destroy the spirochetes, could not penetrate the biofilm (Figure 3) and attacked the surrounding tissue instead . We also alluded to the recent work showing how the adaptive immune system became involved after traumatic brain injury and very rapidly created much more devastating damage than the innate immune system .
Our other observation, which combined pathology and immunopathology was demonstrating the co-localization of beta amyloid (Aβ) and biofilm  (Figure 4). The significance of the finding represented by that photomicrograph was not alluded to. We present herein observations and marshal the evidence that gives substantiation to the significance of that finding.
Aβ has been shown, in a 3-dimensional pathology (side-by-side) presentation, to lay on top of the biofilms  (Figures 5 and 6). This finding, plus the aforementioned co-localization, positions the Aβ in direct contiguity with the biofilms (which actually form the pathological plaques of AD).
An issue that remains is: how does the Aβ become positioned there, and what is its potential purpose?
We believe it may be related to the presence of TLR 2. This innate immune system molecule kills by activating the MyD88 pathway which leads to NFκB and ultimately to TNFα . It is the TNFα that is the “killing” agent for TLR 2. (Figure 7). It is capable of destroying planktonic gram positive organisms, yeasts, and spirochetes.
TNFα has been shown to be cleaved by TNFα converting enzyme (TACE) which has been shown to be dramatically upregulated in AD (Figure 8). TACE is localized in the neuronal membranes where it is in direct proximity to the spirochetal derived biofilms and where it acts to upregulate alpha secretase . Beta secretase, and gamma secretase are upregulated by NFκB [11,12]. NFκB then links with BACE (beta amyloid converting enzyme) that cleaves the amyloid precursor protein (APP) that changes the precursor molecule to Aβ . The γ- secretase has been linked to the genetic form of the disease .
Aβ has been shown to be antimicrobial . It seems that is its purpose for which it is generated. However, and this is most important, it is not able to penetrate the biofilm either (just as TNFα cannot).
Thus, the body in trying to rid itself of the spirochetal parasites in one case (TNFα) most assuredly contributes to the disease. In the other case, while also trying to act anti-microbially, the innate immune system creates a substance (Aβ) that further damages the tissue and the neuronal circuits.
As has been said previously, it is most important to treat these microbes before they get to the brain or before the do damage (make biofilms) .
All that is necessary is an antibiotic that is bactericidal and crosses the blood brain barrier. If necessary, a biofilm dispersing agent that also crosses the blood-brain barrier, such as a furan, a pyrrole, a piperidine, or a thiophene or other [16-19] could also be added to the regimen (All these pharmaceuticals cross the blood brain barrier). The spirochetes, biofilm, immune system, and Aβ are capable of marked neuronal damage which is non-reversible. This makes treatment and potential prevention both urgent and compelling.
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