I work in the neurotech/sleeptech space, and Alzheimer’s is one of the endpoints we’re working toward.
On a first read, it seems the authors frame everything through a circadian lens. Their view is that circadian genes regulate glial function, and that when those rhythms are disrupted, clearance breaks down, inflammation increases, and amyloid accumulates, contributing to Alzheimer’s.
There’s another perspective in sleep science that looks at restorative function. The physiological work of sleep like slow-wave activity and glymphatic flow which may be the driver. From that view, amyloid build-up impairs glymphatic clearance, creating a downward spiral of poorer clearance and more accumulation.
Circadian timing is certainly an important modulator, but it’s not the whole story. Without EEG or even basic sleep-wake data, it’s hard to know whether the changes in circadian” gene expression reported here reflect intrinsic clock disruption or simply reduced slow-wave restorative function in these mice.
I've linked to two research papers[2],[3] in AD which are working with the same principles of our work at https://affectablesleep.com
The title is a bit link-bait. It should really be "Disrupting circadian rhythms of plaque-clearing brain cells is associated with Alzheimer's"
> He found that too much of YKL-40, which is linked to Alzheimer’s risk in humans, leads to amyloid build-up, an accumulation that is a hallmark of the neurodegenerative disease.
There are countless studies that highlight how genetics or lifestyle and other factors that result in a reduction of estrogen signaling are associated with Alzheimer's. Estrogen, primarily activated at night decreases the expression of the YKL-40 gene. All of the known interventions, from vitamin D, Mg, to gut, choline, etc all can improve estrogen signaling, decreasing YKL-40 gene. One can end up with Alzheimer's from many different routes so interventions depend on the person.
If there was a pill on the market today that would only increase the plaque-clearing all this really does is move the needle, they still have reduced estrogen signaling and the next weakest part of the system would fail such as from animpaired immune system and they will probably die of pneumonia.
But we could back up and say what is the most common cause of the global reduced estrogen signaling? Often increased oxy-androgens (which increase as we age), so for example 11-ketotestosterone (11-KT) which can't convert to its estrogen form results in upregulates HSD17B2. Why do we have so much inflammation causing increased oxy-androgens from the adrenals? Senescence cells releasing inflammatory factors SASP. More time more time spent on repair resulting in identity loss and mesenchymal drift. All a fancy way of saying we get older and will probably die from whatever weakest part of the system we have genetically. Fix one thing and something else breaks instead.
And for those that want to bring in the most well known genetic mutation APOE e4: APOE e4/e4 has elevated choline demands hindering estrogen signaling as well as raising HDL and lowering LDL. Low estrogen influences Cholesteryl Ester Transfer Protein, raising HDL and lowers LDL beyond what e4/e4 does by itself. With less choline and less phosphatidylcholine, it decreases GLUT1 transporters reducing glucose entering the brain. All of the above leads to an escalating amyloid plaque burden. Then reduced deep sleep and the glymphatic system cleaning is reduced too and you have Alzheimer's.
The above was just from memory probably had an error, but the point is Alzheimer's is not "simple" like this article pretends.
There was a study[0] connected to videos[1] of particular flashing that trigger plaque-clearing rhythms in the brain.
Maybe placebo but my mind feels quietly clearer after watching. It could be that simply slowing down and clearing my mind for that time would do the same.
As usual with Alzheimer's studies, this is another "breakthrough" in mice. Unfortunately, every other Alzheimer's breakthrough in mice has failed to replicate in humans, because... Mice don't get Alzheimer's. We can create mice with dementia patterns that are surface-level similar to Alzheimer's (beta amyloid plaques!), and clear the plaques and even often reverse the dementia. Unfortunately this doesn't help much of anything, since those diseases we create in mice are not Alzheimer's and appear not to actually be similar causally to Alzheimer's. All of them have failed to replicate and we have many of them.
I generally wouldn't trust any Alzheimer's "breakthroughs" in mice models. The models are not accurate and have thus far had zero predictive power for actual Alzheimer's in humans.
Alzheimer's disrupts circadian rhythms of plaque-clearing brain cells
(medicine.washu.edu)199 points by gmays 26 October 2025 | 41 comments
Comments
I work in the neurotech/sleeptech space, and Alzheimer’s is one of the endpoints we’re working toward.
On a first read, it seems the authors frame everything through a circadian lens. Their view is that circadian genes regulate glial function, and that when those rhythms are disrupted, clearance breaks down, inflammation increases, and amyloid accumulates, contributing to Alzheimer’s.
There’s another perspective in sleep science that looks at restorative function. The physiological work of sleep like slow-wave activity and glymphatic flow which may be the driver. From that view, amyloid build-up impairs glymphatic clearance, creating a downward spiral of poorer clearance and more accumulation.
Circadian timing is certainly an important modulator, but it’s not the whole story. Without EEG or even basic sleep-wake data, it’s hard to know whether the changes in circadian” gene expression reported here reflect intrinsic clock disruption or simply reduced slow-wave restorative function in these mice.
I've linked to two research papers[2],[3] in AD which are working with the same principles of our work at https://affectablesleep.com
[1] https://doi.org/10.1038/s41593-025-02067-1 [2] https://doi.org/10.1016/j.jagp.2024.07.002 [3] https://doi.org/10.1093/ageing/afad228
> He found that too much of YKL-40, which is linked to Alzheimer’s risk in humans, leads to amyloid build-up, an accumulation that is a hallmark of the neurodegenerative disease.
There are countless studies that highlight how genetics or lifestyle and other factors that result in a reduction of estrogen signaling are associated with Alzheimer's. Estrogen, primarily activated at night decreases the expression of the YKL-40 gene. All of the known interventions, from vitamin D, Mg, to gut, choline, etc all can improve estrogen signaling, decreasing YKL-40 gene. One can end up with Alzheimer's from many different routes so interventions depend on the person.
If there was a pill on the market today that would only increase the plaque-clearing all this really does is move the needle, they still have reduced estrogen signaling and the next weakest part of the system would fail such as from animpaired immune system and they will probably die of pneumonia.
But we could back up and say what is the most common cause of the global reduced estrogen signaling? Often increased oxy-androgens (which increase as we age), so for example 11-ketotestosterone (11-KT) which can't convert to its estrogen form results in upregulates HSD17B2. Why do we have so much inflammation causing increased oxy-androgens from the adrenals? Senescence cells releasing inflammatory factors SASP. More time more time spent on repair resulting in identity loss and mesenchymal drift. All a fancy way of saying we get older and will probably die from whatever weakest part of the system we have genetically. Fix one thing and something else breaks instead.
And for those that want to bring in the most well known genetic mutation APOE e4: APOE e4/e4 has elevated choline demands hindering estrogen signaling as well as raising HDL and lowering LDL. Low estrogen influences Cholesteryl Ester Transfer Protein, raising HDL and lowers LDL beyond what e4/e4 does by itself. With less choline and less phosphatidylcholine, it decreases GLUT1 transporters reducing glucose entering the brain. All of the above leads to an escalating amyloid plaque burden. Then reduced deep sleep and the glymphatic system cleaning is reduced too and you have Alzheimer's.
The above was just from memory probably had an error, but the point is Alzheimer's is not "simple" like this article pretends.
Maybe placebo but my mind feels quietly clearer after watching. It could be that simply slowing down and clearing my mind for that time would do the same.
[0]: https://journals.plos.org/plosbiology/article?id=10.1371/jou...
[1]: https://vimeo.com/1023275135/378186db55
Previous HN discussion: https://news.ycombinator.com/item?id=41942096
"Circadian cycles impact Herpes Simplex Virus (HSV) infection by influencing both the host's immune response and the virus's replication."
Update: I'm no expert in any of this. Just thinking aloud. Would love some much smarter HN community to speak up on the topic.
I generally wouldn't trust any Alzheimer's "breakthroughs" in mice models. The models are not accurate and have thus far had zero predictive power for actual Alzheimer's in humans.