[HN Gopher] Alzheimer's disrupts circadian rhythms of plaque-cle...
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Alzheimer's disrupts circadian rhythms of plaque-clearing brain
cells
Author : gmays
Score : 120 points
Date : 2025-10-26 17:40 UTC (5 hours ago)
(HTM) web link (medicine.washu.edu)
(TXT) w3m dump (medicine.washu.edu)
| latchkey wrote:
| There has been a bunch of studies connecting Alzheimers to HSV
| and now this potentially connects it back?
|
| "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.
| cjbgkagh wrote:
| Are we sure on the causality here? Many people get chronic
| fatigue from a mono infection (EBV) and chronic fatigue has a
| dysautonomia componenent which has a circadian rhythm
| component. A lot of this stuff is bidirectionally related,
| forming a reinforcing loop.
| kakacik wrote:
| What about heredity of some types of Alzheimer?
| anon84873628 wrote:
| What you'll see repeatedly in the comments on articles like
| this is that Alzheimer's is more of a shared endpoint of many
| different root causes. Usually one person is complaining that
| the research is focusing on the wrong cause, or only treating
| symptoms, or misrepresenting the problem, etc etc. While
| other are defending it is important incremental understanding
| within one part of a very large space. (Oh and don't forget
| the people complaining about mouse research in the first
| place).
|
| What I'm learning from these articles is that Alzheimer's
| results when certain processes fail and negative feedback
| loops begin. That could be due to a genetic issue (and thus
| is heritable as you mention), or an immune response (and thus
| correlated with HSV infection), a toxin, a sleep disorder,
| whatever. In some cases disrupting the loop maybe be enough
| to restore function. In others we need to understand the
| unique root causes. There are many areas to explore and
| disentangle.
| bookofjoe wrote:
| The Genetics of Alzheimer Disease (2012)
| https://pmc.ncbi.nlm.nih.gov/articles/PMC3475404/
|
| New insights into the genetic etiology of Alzheimer's disease
| and related dementias (2022)
| https://www.nature.com/articles/s41588-022-01024-z
|
| The complex genetic architecture of Alzheimer's disease:
| novel insights and future directions (2023) https://www.thela
| ncet.com/journals/ebiom/article/PIIS2352-39...
|
| Towards cascading genetic risk in Alzheimer's disease (2024)
| https://academic.oup.com/brain/article/147/8/2680/7685999
| mobilejdral wrote:
| 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.
| Obscurity4340 wrote:
| What is the word on the best current and ubiquitous
| prophylactics, like you said Vit D(3?)
| mobilejdral wrote:
| For this particular situation on D3 I personally (who is not
| your doctor) would go with vitamin D3-loaded nanoemulsion.
| The reason is that Vit D influences how tryptophan is
| converted down the 5-HTP and serotonin path or the Kynurenine
| path. We want higher serotonin AND specifically in the brain.
| The higher serotonin means better melatonin which not only
| increase sleep, but increase the ERa expression which we are
| trying to increase... in the brain.
|
| There is a recent study on this showing how this form can
| provide better results in the brain. https://www.sciencedirec
| t.com/science/article/pii/S305047402...
|
| In general: Omega-3, bcomplex with choline etc all have
| studies. Really it depends on the individual and what their
| genetic weakest issue is. Its old and boring, but eat
| healthy, don't eat before bed, exercise (dance!), and get
| good sleep always apply.
| Obscurity4340 wrote:
| Are you aware of any association with stimulant treatment
| re alzheimers? Probably the sleep?
| DarkmSparks wrote:
| last I heard everything amyloid/plaque burden was suspect
| after
|
| https://www.nytimes.com/2023/07/19/us/stanford-president-
| res...
|
| It looks very much like they are a symptom rather than a
| cause. They have got very good at medicines that remove
| amyloid/plaques, they only physical outcome was massive brain
| bleeds and death, plus a little
|
| https://www.ncbi.nlm.nih.gov/search/research-news/13804/
|
| before being withdrawn for all the reasons they resigned
|
| https://www.pharmaceutical-technology.com/analyst-
| comment/bi...
|
| absolute disaster :(
| freddie_mercury wrote:
| Not really true. See for instance this link
|
| "Opponents call the amyloid hypothesis zombie science,
| propped up only by pharmaceutical companies hoping to sell
| off a few more anti-amyloid me-too drugs before it
| collapses. Meanwhile, mainstream scientists . . . continue
| to believe it without really offering any public defense.
| Scott was so surprised by the size of the gap between
| official and unofficial opinion that he asked if someone
| from the orthodox camp would speak out in its favor."
|
| https://www.astralcodexten.com/p/in-defense-of-the-
| amyloid-h...
| DarkmSparks wrote:
| From that link
|
| "and only slow progression a relatively small amount."
|
| They don't even do that. they _do_ remove plaques, they
| _do not_ have any statistically significant effect on
| MMSE degradation.
|
| plus I only see the comments that point out the entire
| scientific basis for them was based on faked research.
|
| The way I had it "simply" described was "the plaques are
| basically dead brain cells, the problem is the brain
| cells rapidly dieing, not cleaning up the corpses
| afterwards".
|
| either way, the faked research set dementia research back
| at least 2 decades and wasted billions of dollars on
| failed medications with no benefits and horrific side
| effects (that they tried to cover up).
| yard2010 wrote:
| I'm far from an expert but maybe the air we breathe is toxic?
| It makes stuff oxidize and go bad. It just takes enough of this
| poison and that's it.
| JumpCrisscross wrote:
| > _maybe the air we breathe is toxic?_
|
| I suppose since atmospheric oxygen is mostly of biological
| origin, yes, you're technically correct in labelling oxygen
| in the air as a toxin.
| tyre wrote:
| 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.
|
| [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
| monkeydreams wrote:
| > It could be that simply slowing down and clearing my mind for
| that time would do the same.
|
| Certainly I could not watch this in one, unbroken, session
| without interruption.
| pedalpete wrote:
| Here's a link to the paper [1].
|
| 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
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