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Comment by trendia | Hacker News Reader

In the context of the infectious disease hypothesis, do you know why caffeine / coffee would be associated with lower incidence of Alzheimer's? (It reduces amyloid-beta levels, but if plaques are not the cause of Alzheimer's then this shouldn't provide any protective benefit)

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It's ongoing work for me. Lately I've been digging through a lot of gene expression datasets to try and figure out which genes are the most overexpressed in aging tissues. I then use bioinformatics tools like clue.io to figure out which OTHER genes regulate them, and also possible drugs.

There are a number of pathways that seem to be downregulated by purigenic receptors, many of which are sensitive to adenosine. Caffeine blocks adenosine receptors and blocks signaling.

What could be happening here is suppressing inflammation, since evidently purine nucleotides activate some immune cells.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2568887/

Its not difficult to come up with mechanisms like that, not even difficult to come up with the idea and then get some evidence consistent with it. The key is to make sure everything works out quantitatively: https://www.ncbi.nlm.nih.gov/pubmed/12242150

So this theory holds for caffeine, not specifically coffee? I'm not sure why, but I was under the impression that it was specifically coffee that could be tied to lower incidence of Alzheimers.

Can’t it be as simple as caffeine boosts your metabolism and mutes blood sugar spikes?

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