My post from two days ago was about a 2024 paper that had just won an award from the Alzheimer’s Association.  It found and confirmed some subtle genetic risk factors for PSP.  One of them has to do with the part of the immune system called the complement cascade because it complements the role of antibodies. 

The finding on the complement-related gene prompted me to update my theory of the cause and pathogenesis (the subsequent sequence of events in the brain) of PSP.  That includes exposure to metals, at least in some cases. 

In response to that, a commenter asked which specific metals I had in mind. I responded directly in the comments section, but I thought it would make a good post for today:

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We don’t know which specific metals might be involved in the cause of PSP, or how important they would be relative to other causes we don’t yet understand

• The formal case-control surveys implicating metals asked about metals in general. Besides, that association was weak and lost statistical significance after other exposures were accounted for as confounders.
• US Army veterans who developed PSP years later were more likely to have frequently fired weapons during their service than other Army veterans without PSP. So that incriminates lead, but gunfire undoubtedly aerosolizes other metals as well. My quick search reveals that gunfire can aerosolize aluminum, antimony, barium, cadmium, chromium, copper, iron, lead, manganese, nickel, tin, tungsten and zinc.
• The PSP cluster in a couple of adjacent industrial towns in France suggests chromium, but that’s only the most important of the many metals contaminating that environment. Others with circumstantial associations are arsenic, copper and nickel, but others must exist as well.
• The metals that caused PSP-susceptible cultured neurons to develop tauopathy in a 2020 lab study were chromium and nickel, but other metals weren’t tested because of insufficient lab capability at that time.

So that’s it, and it’s not much. It would be great if the existing genetic risk data could be analyzed for genes involved in metals detoxification. They might have fallen below the threshold of statistical significance for a genome-wide study, but a much more focused gene marker study might be able to show an association with the disease.

It could also be fruitful to analyze available autopsied brain tissue from the French cluster for metals content, comparing it to controls without PSP from the same contaminated area and elsewhere.

Also, let’s not forget that it might take certain combinations of metals, or of metals with other toxins, to increase one’s PSP risk. That could explain why there’s only one known geographical cluster of PSP — that area in France was multiply contaminated.