“Angry” Immune Cells in Brain and Spinal Fluid Identified as Alzheimer Culprit | Hacker News Reader

“Angry” Immune Cells in Brain and Spinal Fluid Identified as Alzheimer Culprit

scitechdaily.com

61 pointskalimanzaro16 comments

First sentence: "The reason your three-pound brain doesn’t feel heavy is because it floats in a reservoir of cerebrospinal fluid". I'm already feeling a little angry!

I started reading this article the other day, read that sentence, and immediately dismissed the article as garbage and moved on.

calm down guys the holidays have been rough but let's keep bringing the big boy energy. Here's a pull quote for you

> “..from the degenerating brain’s microglia cells to enter the brain. It could be the degenerating brain activates these cells and causes them to clone themselves and flow to the brain,” Gate said. “They do not belong there, and we are trying to understand whether they contribute to damage in the brain.”

Interesting result right? Sounds like a definite maybe. Seems like correlation vs causation is really hard with brain degeneration. Sure would be nice to have a grand theory but maybe the theory is death by a thousand cuts. call it the i-dont-even-know-how-many-billion dollar question

The study itself: https://www.cell.com/cell/fulltext/S0092-8674(22)01463-5

Is this correlation or causation? The problem with past approaches appears to be a focus on states that are probably just correlates.

If you run out of correlations, eventually one has to be a causation!

No you don’t, in fact there is absolutely no reason why Alzheimer’s has to have a single cause you can have multiple genetic, environmental and pathogenic factors leading to the condition which eventually exhibits itself as Alzheimer’s.

This is the important insight. Beta amyloids, tau tangles, now angry immune cells. Maybe look into infections that provoke them all?

What we know is that certain vaccinations (Tdap, flu) predict a 40% reduced risk of dementia, and recent treatment with valacyclovir, a herpes treatment, similarly. And autopsies of Alzheimer's patients show brain infections.

What will all the amyloid biochemists do when that whole line of research is abandoned?

WOW, I hadn't seen that about vaccinations. Seems to be a good deal of info from around 2020 about this. One example is https://aaic.alz.org/releases_2020/vaccines-dementia-risk.as....

Unfortunately, again, the vaccines were not applied to a single population as a variable, so there’s no evidence I don’t think to see a causal link: those who seek out such shots are a somewhat unique population

I'm lost, people who seek out flu vaccines are a unique population?

This is an example of the old trope that only random controlled trials (RCTs) can demonstrate causation. It was doctrine enforced until the '90s. Nowadays, statisticians have protocols to extract a causation signal from population studies that are large enough.

That is not to claim lack of vaccination causes dementia. But it means something affected by vaccination does.

When you follow a cohort of 46,000 patients for six years, you get enough good data to draw strong conclusions. That the same numbers came out for a disjoint population of 12,000, over the same period, demonstrates it. But statistics only points you in a direction, it is not biochemistry.

My understanding of one guess around e.g. annual flu shots is not so much protection from infection as frequent stimulation of the immune system being beneficial in particular for Apoe4 carriers.

E.g. from p. 329 of Lieberman's Exercised:

> Although Westerners who carry the two copies of a gene called Apoe4 (a protein that transports fats in the bloodstream) are three to fifteen times more likely to get Alzheimer's in old age, elderly Tsimane with the same ApoE4 gene are less likely to show declines in cognitive performance if they suffer from many infections.

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I have heard something similar about ApoE4 carriers in Nigeria though don't have a source on hand. Basically a lot of variations of the hygiene hypothesis and possibly compatible with "angry immune cells". Definitely not a "mystery solved" though.

Could inflammation from particulate pollution [0] be one of the factors underlying these "angry" immune cells?

[0] https://pubmed.ncbi.nlm.nih.gov/31746986/

Is this a deathblow to the amyloid hypothesis?

didn't we already know it's "angry" immune cells, all along ? Or was this some buried insight

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