Reaction of Amyloid-β Peptide Antibody with Different Infectious Agents Involved in Alzheimer’s Disease

Abstract

As early as the 1980s, molecular virologist Ruth Itzhaki began to investigate if there was a causal connection between infections and neurodegenerative disorder. Although the theory has yet to be universally embraced, in 2016 Itzhaki and 33 other scientists from all over the world published a review article in this very journal presenting evidence for the causal role of pathogens in Alzheimer's disease (AD). Exactly how and in what way pathogens affect the induction of AD has yet to be determined, but one possible answer may involve the cross-reactivity of different pathogens with amyloid-β (Aβ). Aβ autoantibodies have been detected in the serum and cerebrospinal fluid of AD patients and in some healthy individuals. In the present study our major goal was to investigate whether antibodies made against Aβ would react both with other brain proteins as well as pathogens associated with AD as a result of molecular mimicry or the binding of bacterial toxins to Aβ42. Our study used a specific monoclonal antibody made against Aβ42, which not only reacted strongly with Aβ42, tau protein, and α-synuclein, but also had from weak to strong reactions with 25 different pathogens or their molecules, some of which have been associated with AD. The homology between peptide stretches of microbial origin and proteins involved in AD could be a mechanism by which antibodies to homologous peptides mount attacks against autoantigens in AD. We concluded that bacterial molecules bind to Aβ protein, forming small oligomers, then encasing pathogens and their molecules to form amyloid plaques, the tell-tale markers of AD. Conversely, these same Aβ peptides induce the production of antibodies to both Aβ42 and bacterial molecules, which may inhibit bacterial pathogenesis, but in the process may promote amyloid plaque formation.

Amyloid-Beta 1-42 Cross-Reactive Antibody Prevalent in Human Sera May Contribute to Intraneuronal Deposition of A-Beta-P-42

“…In addition to the importance of BBB compromise, it is crucial to find the origin of the AßP-42 cross-reactive antibodies that are detected in the blood of healthy subjects and AD patients. In our earlier studies [ 47 ] we showed several pathogens and antigens such as LPS, bacterial cytolethal distending toxin, and others that may contribute to the presence of AßP-42 cross-reactive antibodies. The identification of environmental triggers that cross-react with AßP-42 antibodies and contribute to amyloidogenesis may help clinicians to develop treatment protocols involving the removal of these triggers.…”

“…In our earlier study [ 47 ] we showed that these brain-reactive autoantibodies may originate from cross-reactive epitopes shared by A β P-42 with different infectious pathogens. Unpublished data from another one of our studies also indicate that these antibodies may be a result of cross-reactivity between A β P-42 and food antigens, and possibly from protein misfolding of A β P-42 by aluminum, heavy metals, and other toxic chemicals.…”

Correlation between Antibodies to Bacterial Lipopolysaccharides and Barrier Proteins in Sera Positive for ASCA and ANCA

“…This elevation of serum level of zonulin and other tight junction proteins indicates that intestinal permeability may be responsible for neurological complications of IBD [23]. At the BBB, S100B and claudin-5 are the most enriched proteins, and their dysfunction has been implicated in neuroinflammatory disorders such as MS, neurodegenerative diseases such as Alzheimer's, and psychiatric disorders including depression and schizophrenia [56,57,106,107].…”

“…Recognized as the great inducer of neuroinflammation, LPS injections have been used in multiple animal models of neurological disorders from autism spectrum disorders to multiple sclerosis [32,33,37,[50][51][52][53][54][55]. Furthermore, LPS antibodies have been found in the sera of patients diagnosed with Alzheimer's disease, chronic fatigue, major depression, and schizophrenia [56][57][58][59][60]. Individuals with IBD have been shown to have increased blood levels of LPS [61][62][63]; therefore, they would be at greater risk for a breach of the BBB and neuroautoimmunity.…”

Reaction of food‐specific antibodies with different tissue antigens

“…However, immune reaction between anti‐corn antibody and ten out of sixty‐five tested tissue antigens, as shown in Fig. , indicates that immune reaction by these tissue antigens with corn proteins may play a role in additional autoimmunities, such as intrinsic factor in pernicious anaemia, thyroid peroxidase (TPO) in thyroid autoimmunity, alpha‐myosin in cardiovascular autoimmunity, tyrosinase in autoimmune vitiligo, and neurotrophin in MS, alopecia areata and Alzheimer’s disease (Botchkarev, ; Ongenae et al , ; Lv et al , ; Andres & Serraj, ; Kalinowska‐Lyszczarz & Losy, ; Fröhlich & Wahl, ; Vojdani et al , ). With regard to reactivity between anti‐soy antibody and different tissue antigens, the reaction was strongest with tyrosinase, intrinsic factor and alpha‐enolase, which are known to be involved in pernicious anaemia, vitiligo and rheumatoid arthritis (RA) (Ongenae et al , ; Lundberg et al , ; Andres & Serraj, ).…”