Alzheimer's disrupts circadian rhythms of plaque-clearing brain cells

mobilejdral

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.

yard2010

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

> *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.

Obscurity4340

What is the word on the best current and ubiquitous prophylactics, like you said Vit D(3?)

mobilejdral

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 ERα 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.sciencedirect.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

Are you aware of any association with stimulant treatment re alzheimers? Probably the sleep?

latchkey

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

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

What about heredity of some types of Alzheimer?

anon84873628

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.