From what I know about terminal lucidity in alzheimer's patients it seems to me that these plaques act like electrical resistors that increase the impedance for neurotransmission. But chemically of course. So if you push more current through the system, such as when you're dying, you can suddenly access memories that were locked off. Is my understanding correct?
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.
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.
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.)
It's utterly unimportant. It's all research and all progress and all works towards our benefit eventually. The fact that an important discovery is still in the mouse stage and not yet in the human stage doesn't make it any less important or interesting, unless you are unutterably simple.
Put another way: the "in mice" doesn't matter because they are studying alzheimers, not mice. the mice are just the lab equipment of the moment. I don't care what kind of glassware or computers they use either.
It depends on what's being studied. There are mice studies on diet which obviously don't carry over to human beings since we don't have similar digestive systems. It may be true (arguable) that all research data is of some benefit, but don't expect people to be as excited about mouse research as human research.
How do they get the alzheimers mice? Article doesn't say. Usually in studies they take healthy mice and induce the condition artificially. That can be a confounding factor since the condition isn't induced in the specimens we care about (human beings). Is it even the same condition?
It doesn't matter how they give mice alzheimers, or any other condition. That's just part of controlling variables to test for one thing. It also doesn't matter that they were fed processed food rather than having to find things in the wild, unless the effect of diet was the specific thing they were examining.
It does not matter how they give Alzheimer's to a lab mouse providing they give Alzheimer's to a lab mouse – not a different disorder that happens to have the symptoms of Alzheimer's.
If this was a website for fundamental biology research I’d agree.
As it stands, the headline is misleading and clickbaity.
> the "in mice" doesn't matter
Of course it matters, because that has a direct bearing on how applicable it is to humans and how much time it’s likely to take to be of any benefit to humans, if it ever is. That’s the whole point being discussed.
Also see this comment to help understand why “in mice” is a huge qualifier in this case, because mice don’t naturally develop Alzheimer’s: https://news.ycombinator.com/item?id=50218606
I think the important bit is that, from my understanding, mouse models of alzheimer's dont translate as reliably to humans as it does for other diseases
This is correct, mice don’t naturally experience alzheimer’s or other dementias during their lifespans and the structure of their amyloid beta protein is different as well. To continue using them as model organisms, we have to induce the disease in them by either introducing human genes that are linked with alzheimer’s, or chemically inducing a disease state that we believe to be similar. Mice are much better models organisms for studying metabolism or cancer, by comparison.
The "... in mice" qualifier is somewhat overdone, but for Alzheimer's in particular, it's actually extremely important: mice do not experience Alzheimer's. We test Alzheimer's drugs in mice by artificially inducing something that produces similar dementia symptoms, and then seeing how the drugs influence that progression. If that model is different from how Alzheimer's works--and there's pretty decent suggestions from the history of failed Alzheimer's drugs in humans that our models of Alzheimer's are in fact wrong--then anything that fixes that model has suspect utility.
So does this help alleviate the dementia symptoms? Or do those remain but at least the patients get better sleep?
You need to ask the rats.
It is actually possible to test if a rat has dementia, eg:
https://pmc.ncbi.nlm.nih.gov/articles/PMC2895266/
https://currentprotocols.onlinelibrary.wiley.com/doi/10.1002...
From what I know about terminal lucidity in alzheimer's patients it seems to me that these plaques act like electrical resistors that increase the impedance for neurotransmission. But chemically of course. So if you push more current through the system, such as when you're dying, you can suddenly access memories that were locked off. Is my understanding correct?
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.
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.
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.
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.)
> So if you push more current through the system, such as when you're dying [...]
Is this actually the case or are you conjecturing?
...in mice.
Not knocking the research, cure it already! I just think it should be in the title to avoid false hope.
We're adults like you are and can manage both our emotions and the responsibility of understanding that headlines aren't the totality of information.
When it is taking about a breakthrough in treatment of a human disease, it's kind of important if it's not actually in humans
Also "headlines aren't the totality of information" doesn't mean there's no clickbait headlines...
It's utterly unimportant. It's all research and all progress and all works towards our benefit eventually. The fact that an important discovery is still in the mouse stage and not yet in the human stage doesn't make it any less important or interesting, unless you are unutterably simple.
Put another way: the "in mice" doesn't matter because they are studying alzheimers, not mice. the mice are just the lab equipment of the moment. I don't care what kind of glassware or computers they use either.
It depends on what's being studied. There are mice studies on diet which obviously don't carry over to human beings since we don't have similar digestive systems. It may be true (arguable) that all research data is of some benefit, but don't expect people to be as excited about mouse research as human research.
How do they get the alzheimers mice? Article doesn't say. Usually in studies they take healthy mice and induce the condition artificially. That can be a confounding factor since the condition isn't induced in the specimens we care about (human beings). Is it even the same condition?
It doesn't matter how they give mice alzheimers, or any other condition. That's just part of controlling variables to test for one thing. It also doesn't matter that they were fed processed food rather than having to find things in the wild, unless the effect of diet was the specific thing they were examining.
It does not matter how they give Alzheimer's to a lab mouse providing they give Alzheimer's to a lab mouse – not a different disorder that happens to have the symptoms of Alzheimer's.
If this was a website for fundamental biology research I’d agree.
As it stands, the headline is misleading and clickbaity.
> the "in mice" doesn't matter
Of course it matters, because that has a direct bearing on how applicable it is to humans and how much time it’s likely to take to be of any benefit to humans, if it ever is. That’s the whole point being discussed.
Also see this comment to help understand why “in mice” is a huge qualifier in this case, because mice don’t naturally develop Alzheimer’s: https://news.ycombinator.com/item?id=50218606
I think the important bit is that, from my understanding, mouse models of alzheimer's dont translate as reliably to humans as it does for other diseases
This is correct, mice don’t naturally experience alzheimer’s or other dementias during their lifespans and the structure of their amyloid beta protein is different as well. To continue using them as model organisms, we have to induce the disease in them by either introducing human genes that are linked with alzheimer’s, or chemically inducing a disease state that we believe to be similar. Mice are much better models organisms for studying metabolism or cancer, by comparison.
The "... in mice" qualifier is somewhat overdone, but for Alzheimer's in particular, it's actually extremely important: mice do not experience Alzheimer's. We test Alzheimer's drugs in mice by artificially inducing something that produces similar dementia symptoms, and then seeing how the drugs influence that progression. If that model is different from how Alzheimer's works--and there's pretty decent suggestions from the history of failed Alzheimer's drugs in humans that our models of Alzheimer's are in fact wrong--then anything that fixes that model has suspect utility.
No, you cure it already!