THE 3-D Pictorial Spirochetal Pathway to Alzheimer’s Disease

This perspective article features a visual depiction supporting a potential link between spirochetal infection and Alzheimer’s disease (AD). Two-dimensional (2D) images, alongside innovative three-dimensional (3D) imaging derived from 2D photomicrographs, provide the basis for a pathway through which spirochetes travel to the brain, with the hippocampus identified as their initial target. Upon arrival at this specific region, spirochetes can be found both extracellularly and intracellularly. Despite their slow growth, spirochetes eventually create a biofilm. Biofilm formation requires 10 cells in every direction, which can take two or more years for a significant biofilm to develop. To establish the biofilm, the spirochetes produce a slime coating that shields them from antibiotics, the immune system, and harmful irritants. Simultaneously with biofilm formation, spirochetes may induce beta-amyloid precursor protein (AβPP) and beta-amyloid (Aβ) production. In the extracellular space, biofilms can be covered with Aβ to be part of senile plaques. Intracellularly, during biofilm formation, spirochetes also generate amyloid precursors. It can also be hypothesized that spirochetes may induce tau hyperphosphorylation (p-tau), perhaps through a mechanism involving phosphatase inhibition. Accumulation of p-tau prevents the stabilization of microtubules within dendrites, leading to the disintegration of tubules and dendrites. Overall, neurofibrillary tangles are formed that, together with amyloid plaques, contribute to neuronal death. As more dendrites and neurons are destroyed, impulse transmission is impaired, resulting in cognitive deficits.