Considering Alzheimer’s Disease: Possible Mechanisms for Worsening of the Disease

Stroke, diabetes, nicotine, haloperidol, diet soft drinks, and others have all been shown to cause
worsening of Alzheimer’s disease (AD). In the following, we outline a possible mechanism for each of
these entities to cause worsening by impacting a pathway to AD that we have developed based on
our observations and those of others. That pathway includes microbes that make biofilms which
activate the innate immune system; this ultimately leads to tissue destruction. The leading candidates
for the microbes are pathogenic periodontal spirochetes and Lyme spirochetes which we believe are
the driving forces in the formation of biofilms. We show how diabetes and its inherent hyperosmolality
causes worsening of AD because the microbes make more biofilms in the presence of the
hyperosmolar stress. More biofilms lead to more activation of the innate immune system (biofilms
have receptor sites for Toll-like receptor 2 [TLR2]). Also outlined is how the dispersal of biofilms via
nicotine and other commonly ingested/inhaled chemicals and medications leads to more severe
disease.
Consequently, either “making” them as with diabetes, or “breaking” them as with nicotine, results in
more biofilms and more activation of TLR2. Low serum levels of vitamins K2 or D3 lead to
upregulation of TLR2 again causing worsening of the disease from increased innate immune system
activation. Involvement of the adaptive arm of the immune system, in conjunction with biofilms, also
leads to neurologic sequelae. Cerebrovascular accident (CVA), stroke, is the most disastrous
malefactor of all because it is accompanied by activation of the adaptive immune system
(lymphocytes and IgG) after disruption of the blood brain barrier. This creates massive tissue damage
very rapidly. There are many fewer things that make Alzheimer’s disease better when compared to
worsening it. These are briefly mentioned. Early treatment would help prevent not only Abeta, as been
outlined, but also the development of hyperphosphorylated tau. Thus, both the major pathological
findings, Abeta and tau, would be addressed.