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Different Brain Regions Are Infected with Fungi in Alzheimer’s Disease

nature.com

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Re: Different Brain Regions Are Infected with Fungi in Alzheimer’s Disease

#91

Post by chetanahuja »

kevinalexbrown wrote: post #45
chetanahuja wrote: post #37

Earlier quoted context omitted.

The discovery, if corroborated by others, could indeed be huge but I'm afraid it wouldn't open up new treatment options anytime soon. Fungal infections inside the body are really really hard to treat in the first place. Add to that the blood-brain barrier which makes it very hard to treat any type of infection in the brain. https://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrier#Fu... Combination of these two facto…

First, there are antifungal drugs that pass the BBB, with varying efficacy: https://www.medicine.wisc.edu/sites/default/files/domfiles/i... Second, antifungals have positively affected AD-like symptoms, though possibly through misdiagnosis.

I should have put a disclaimer that I'm not a doctor or expert in pharmaceutical research by any means but unfortunately have had to learn a fair bit about fungal infections the hard way due to a loved one having been affected. Antifungal treatments for internal infections are long (of the order of years), can be difficult to administer (some of them can only be done via IV) of uncertain efficacy and can have serious side effects. And this is for organs that don't have to overcome the BBB.

Nonetheless, if some anti-fungal treatments do prove to be effective against alzheimer's it'll be an amazing advance in medicine. Probably at the level of a Noble prize for the researchers. I'd love to see that happen.

Re: Different Brain Regions Are Infected with Fungi in Alzheimer’s Disease

#92

Post by zaroth »

nonbel wrote: post #82
protomyth wrote: post #72

Earlier quoted context omitted.

Haven't we studied the effects of Alzheimers enough not to need the control group? I worked in clinical trials and one study still haunts me knowing what happened to the control group.

Sure, it fits right in with the plan to get rid of those pesky controls when testing painkillers too: "Drug companies have a problem: they are finding it ever harder to get painkillers through clinical trials. But this isn't necessarily because the drugs are getting worse. An extensive analysis of trial data1 has found that responses to sham treatments have become stronger over time, making it harder to prove a drug’…

Comparing old vs new is how it's done in cancer research. It's inhumane to prescribe placebo to someone in serious pain. You give them the old or the new, and they report how they felt.

In this case, since there is no concept of old or new, it's an entirely new class of treatment. So you give the current best-practice treatment without anti-fungal, and you give the same with anti-fungal.

Anyone in the study is agreeing at the onset that they have a 50/50 chance they will either get the current best practice, or the exact same thing but also the anti-fungal. These are volunteers who are helping move the anti-fungal research forward for everyone, in exchange for a chance of getting early access. They can also leave the study at any time after starting, but if they are in the anti-fungal group they would lose access to it if they did.

If that's not enough, there are cases (e.g. in cancer research) of de-blinding the study when there's a clear/strong positive effect and providing early access to all enrolled if it becomes obvious the new treatment is widely beneficial.

So I think we have the theory behind the ethics fairly well wrapped on how to roll out these drugs. I don't think in practice it works so well, the studies are often poorly run and poorly administered making them extremely more costly than they should be.

Re: Different Brain Regions Are Infected with Fungi in Alzheimer’s Disease

#93

Post by captainill »

If you've ever taken antibiotics for an extended period and ended up with a fungal infection due to the loss commensal bacteria this is pretty intriguing. There is a lot of new literature proposing links between gut disruption and neurodegenerative disease.

Re: Different Brain Regions Are Infected with Fungi in Alzheimer’s Disease

#94

Post by vixen99 »

nickff wrote: post #43
low_battery wrote: post #13

Earlier quoted context omitted.

Yeah, but that was in 1982.

Are you implying that doctors have become more accepting of theories which challenge the status quo? Do you have any reason to believe things have gotten better? Doctors still seem to prescribe blood pressure medication and low-salt diets to people with hypertension, depite the overwhelming number of studies which show that neither prescription has any impact on mortality rates. It doesn't look like they are particul…

No impact? What about the SPRINT study ("Will lower blood pressure reduce the risk of heart and kidney diseases, stroke, or age-related declines in memory and thinking?" - 'largest study ever') was discontinued when it 'produced significant results' with the risk of death down by almost a quarter? I presume that blood pressure lowering was effected by drugs. Please clarify your comment because on the face of it (I have no expert knowledge, you may have) it seems to be quite wrong.

Re: Different Brain Regions Are Infected with Fungi in Alzheimer’s Disease

#96

Post by falsedan »

calinet6 wrote: post #57
falsedan wrote: post #48

Earlier quoted context omitted.

Doctors are selected and trained to memorize insane amounts of facts, and how to match symptoms to facts. Updating those facts is hard since they're stored when the brain is young and still great at learning (there are refresher courses doctors are required to attend to keep their accreditation, but they lean heavily towards learning new facts, not changing existing ones).

This doesn't apply as cleanly to research, however, where the whole point is to discover new facts.

Well, medical researchers aren't doctors (they can't proscribe medication or perform medical procedures).

Re: Different Brain Regions Are Infected with Fungi in Alzheimer’s Disease

#97

Post by dnautics »

moyix wrote: post #79
niels_olson wrote: post #18

Hi, I do research using the same methods: immunohistochemistry. This was done with rabbit polyclonal antibodies. The key being polyclonal. We don't know what those antibodies are really staining. The difference, however, is intriguing.

Could you elaborate on what polyclonal means here? Does it mean that they might not have detected fungus after all, but some other thing that would activate the same antibodies?

Yeah, but that's true for monoclonals too, just a matter of degree.

A polyclonal antibody is an extraction of (usually rabbit) blood from an animal that has been insulted with the agent you'd like to detect. The extraction is enriched for antibodies. They are less reliable, because there could also be other antibodies in there. Even the antibodies that recognize what you're looking for could be a population of antibodies, each recognizing a different part (think the blind men and the elephant parable). Presumably, you have tested that a positive control of what you're trying to look for works.

A monoclonal is different. You insult a mouse with a sample of what you'd like to detect, and then resect the spleen, which contains b-cells, cells that produce the antibody. You then fuse the b-cells with a special strain of cancer cell that will immortalize the b-cell (these are called 'hybridomas'). After sorting one cell to a well, you then test to see if the cells in the well have produced an antibody that detects what you're looking for. Therefore, you can be confident that a monoclonal antibody contains only one antibody, that recognizes only one antigen.

You don't necessarily know what the antigen is that is recognized (that's called the epitope). The epitope could be, say, a piece of protein on the outside of the fungus or a different piece of protein on the outside of the fungus. It's even conceivable that even for a monoclonal there are side-reactions against things that are naturally in the sample.

And: Epitope retrieval techniques are really complicated. So figuring out exactly what epitope is recognized is not trivial.

Re: Different Brain Regions Are Infected with Fungi in Alzheimer’s Disease

#98

Post by [deleted] »

moyix wrote: post #79
niels_olson wrote: post #18

Hi, I do research using the same methods: immunohistochemistry. This was done with rabbit polyclonal antibodies. The key being polyclonal. We don't know what those antibodies are really staining. The difference, however, is intriguing.

Could you elaborate on what polyclonal means here? Does it mean that they might not have detected fungus after all, but some other thing that would activate the same antibodies?

[deleted]

Re: Different Brain Regions Are Infected with Fungi in Alzheimer’s Disease

#99

Post by nonbel »

dnautics wrote: post #97
moyix wrote: post #79

Earlier quoted context omitted.

Could you elaborate on what polyclonal means here? Does it mean that they might not have detected fungus after all, but some other thing that would activate the same antibodies?

Yeah, but that's true for monoclonals too, just a matter of degree. A polyclonal antibody is an extraction of (usually rabbit) blood from an animal that has been insulted with the agent you'd like to detect. The extraction is enriched for antibodies. They are less reliable, because there could also be other antibodies in there. Even the antibodies that recognize what you're looking for could be a population of antibo…

>"you can be confident that a monoclonal antibody contains only one antibody, that recognizes only one antigen"

Not sure if you really meant that since it is kind of contradicted by some later statements, but all antibodies are promiscuous. Thinking you can map one antibody to one epitope is extremely dangerous. It is a matter of quantity (affinity/avidity), not quality.

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