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.
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.
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