More Theorizing on the Role of Pathogens in Alzheimer's Disease
The dominant approach to Alzheimer's research and the development of potential therapies involves finding ways to clear out aggregates of amyloid and tau that build up in the brain. This has proven challenging, however. It is too early to say in certainty whether lack of tangible progress on this front is because it is a hard problem, or because this isn't the most effective direction. The weight of evidence strongly suggests the former is the case, but that hasn't stopped delayed progress from spurring the development of a great many alternative hypotheses as to the cause of Alzheimer's disease. One line of thinking suggests that pathogens are more important than presently accepted to be the case, and paints Alzheimer's disease as a consequence of the progressive age-related failure of the immune system to deal with specific types of invading microbe. The paper here is one example of the type.
The infectious nature of Alzheimer's disease (AD) was revealed when spirochetes (both dental and Lyme) were shown to be present in the brains of affected patients. The dental microbes travel from the oral cavity during times of disruption of the dental plaque and subsequent bacteremia following dental procedures. Lyme borrelia travel to the brain via the blood stream during the secondary stage of that disease. The spirochetes have an affinity for neural tissue and pass through the blood-brain barrier easily. Once the spirochetes are in the brain, they attach, divide (albeit very, very slowly), and multiply. When they reach a quorum, they begin to spin out a biofilm. Because of the exceedingly slow division, it takes approximately 2 years to accumulate sufficient organisms to make one biofilm. At some point after attachment and formation of the biofilms, the innate immune system becomes activated and attempts to destroy them.
The innate immune system first responder, Toll-like receptor 2, generates both NF-κB and TNF-α which try to kill the spirochetes in the biofilm, but cannot penetrate the "slime". NF-κB is also responsible for the generation of amyloid-β (Aβ) which itself is anti-microbial. Aβ cannot penetrate the biofilm either, and its accumulation leads to destruction of the cerebral neurocircuitry. Where spirochetes have been found in the brains of Alzheimer's disease (AD), it may be considered an infectious disease. Treatment with a bactericidal antibiotic with a concomitant biofilm disperser seems most reasonable; but any neurologic damage is irreversible. It is therefore of the utmost importance to treat early in the course of this disease.
It seems that brains must be organized to preserve function of the important areas as long as possible, the brainstem andhypothalamic regions in those that have them.
When we see things like Exosomal transfer of RNA I would encourage us to think mitochondrial transfer instead as that is more likely what the experimenters are getting at. Trust me.
The question then is what are the major circuits that bring the appropriate mitochondrial-exosomal packages into the hub of the hypothalamus, and what circuits express them out.
Here's another paper with more evidence for AD having an infectious component.
http://journal.frontiersin.org/article/10.3389/fnagi.2017.00195/full
(16S rRNA Next Generation Sequencing Analysis Shows Bacteria in Alzheimer's Post-Mortem Brain)
They also cite some other work with different bacterial species, mostly originating from either the oral or gut microbiome. The general picture they draw is a combination of a breakdown of the blood-brain barrier due to age combined with poor hygiene.