Comment by unification_fan

Plaques probably/likely affect local neurotransmission in close proximity of a plaque. But plaque load does not correlate well with dementia severity, and removing plaques entirely (which we can now do very well) does not prevent further cognitive decline (and appears to have very little effect at all).

Plaques, however, do lead to an aggravated response by the immune-equivalent cells in the brain (microglia). There has been a lot of interest in how much this microglia response to plaques triggers some of the symptoms of AD, and this what the research summarised in TFA is interested in also. Despite what TFA implies (it's an overcooked Uni press release) there's been heaps of interest in microglia over the last few years in the AD space.

Ultimately, we still don't know what causes the majority of AD symptoms, and this is a very controversial space. Historically, a number of AD researchers (including one very prominent researcher) staked their reputation on plaques being fully or mostly causative, and refuse to let go of this idea despite the growing body of contrary evidence -- which has created a bit of cognitive hysteresis in the field (and led to vast amounts of arguably wasted pharma R&D). It was a good idea at the time as it was the obvious, most parsimonious explanation; but biological reality has a habit of not conforming with Occam's razor, sadly.

(As for terminal lucidity -- this is not my field; IIUC it's also debated, but your idea is not entirely at odds with one theory. There are many theories, and it's not entirely accepted that this even reliably occurs at all.)

Even prior to this study I've seen people post memes about terminal lucidity. In subsequent discussion people have said it's related to the immune system finally giving up, reducing inflammation, leading to increased perceived health. And then you die from what the immune system was keeping at bay.

So this study ties in neatly with that.

> So if you push more current through the system, such as when you're dying [...]

Is this actually the case or are you conjecturing?

Generally yes, but I think it's a lot more nuanced and varied than that.

My guess is that there are a large set of genetic, environmental, and idiopathic contributors that converge to a loosely similar phenotype, but couldn't be treated effectively in the same way because they have different sets of causes.

I think we'll eventually get to a point where we can treat many kinds of dementia in the same way we treat infections/etc... But it'll take a while.

One of the fraud filled paths in science.

More like rust, where once it starts it allows the process to speed up. In this case collecting poisons.