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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

#141

Post by tptacek »

pohl wrote: post #128
carbocation wrote: post #125

If Alzheimer's Disease (AD) is caused by fungal infection, why have antifungals (often given for people with invasive fungal disease) never cured an AD patient? AD is common enough that many of these people will have received antifungals for e.g. esophageal thrush or even fungemia. Regarding the research, the data presented here are not convincing without larger scale replication with better controls and more standar…

Good question. Are anti fungal molecules small enough to cross the blood brain barrier easily?

Yes, a bunch of them, including fluconazole, which is a first-line treatment for common fungal infections.

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

#142

Post by protomyth »

toast0 wrote: post #138
protomyth wrote: post #126

Earlier quoted context omitted.

The place where I worked did a pretty good job at administering the studies. The cost was in all the sampling and shipping. When your study is doing 1,000 sample kits with 5 samples every week day for multiple years, its going to cost. I am still a bit clueless with all the research we have done with Alzheimer's why we need another control group?

The control group, with double blinds, provides evidence that the change in treatment causes the change in outcome. If you test without a control, the change in outcome could be a result of any other changes between the test protocol and previous control groups. You might be able to do a small study without a control to test feasibility of the hypothesis, but I don't know if that would pass ethics review; would proba…

Here's my problem, we know the outcome of Alzheimer's, surly we have the data to go ahead without a control group? We've had them before.

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

#143

Post by toast0 »

protomyth wrote: post #142
toast0 wrote: post #138

Earlier quoted context omitted.

The control group, with double blinds, provides evidence that the change in treatment causes the change in outcome. If you test without a control, the change in outcome could be a result of any other changes between the test protocol and previous control groups. You might be able to do a small study without a control to test feasibility of the hypothesis, but I don't know if that would pass ethics review; would proba…

Here's my problem, we know the outcome of Alzheimer's, surly we have the data to go ahead without a control group? We've had them before.

Without the control group, you don't know if the change you think you made is the change that made a difference.

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

#144

Post by DanBC »

toast0 wrote: post #143
protomyth wrote: post #142

Earlier quoted context omitted.

Here's my problem, we know the outcome of Alzheimer's, surly we have the data to go ahead without a control group? We've had them before.

Without the control group, you don't know if the change you think you made is the change that made a difference.

The control is either "no treatment" or "treatment as usual".

Those have problems of blinding, and treatment vs no treatment is difficult to get through ethics committees.

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

#145

Post by carbocation »

tankenmate wrote: post #133
carbocation wrote: post #125

If Alzheimer's Disease (AD) is caused by fungal infection, why have antifungals (often given for people with invasive fungal disease) never cured an AD patient? AD is common enough that many of these people will have received antifungals for e.g. esophageal thrush or even fungemia. Regarding the research, the data presented here are not convincing without larger scale replication with better controls and more standar…

One possible reason I can think of is that the immune system in the brain is somewhat different from the rest of the body; not quite on par with say the mammary glands, testes, or eyes. Obviously I am not a doctor etc, anti biotics etc can have reduced effect in body parts that have reduced or modified immune responses; maybe anti fungals are similar?

It is true that medication penetration of the blood-brain barrier and delivery to the brain is different from other organs (each organ has unique characteristics in this regard).

But we do treat people with CNS infections routinely, including CNS fungal infections.

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

#146

Post by tim333 »

Geeek wrote: post #139
tim333 wrote: post #127

I was thinking if this is real then there must have been past cases of people with Alzheimer’s having been given antifungals for other reasons and having gotten better. Googling randomly I came across one, sadly paywalled but from the abstract the guy had been diagnosed with Alzheimer's for three years, then they figured it was cryptococcal meningitis and gave antifungals and four months later he was normal. The inte…

Here you go http://www.docdroid.net/PBdotNO/contentserver.pdf.html

Thanks

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

#147

Post by nonbel »

jschwartzi wrote: post #131
nonbel wrote: post #67

I bet if they double stain with anti-amyloid-Beta they will see the staining overlap. They just say they used "antibody raised against proteins obtained from C. glabrata, C. famata, C. albicans, P. betae and S. racemosum", so they don't even know (or want to say) what these antibodies react with... Amyloids have generic secondary structure (can be created from any amino acid sequence under the right conditions) and y…

Do the amyloid proteins you'd expect concentrate in similarly-shaped groupings? One claim is that the shape of the stains has fungal morphology. If Amyloid-beta concentrations can have fungal morphology then I would think that might strengthen your claim and weaken the paper's. I'm only an engineer though, so feel free to dismiss me as ignorant of your field. Either way I can see how these findings are not terribly i…

>"One claim is that the shape of the stains has fungal morphology. If Amyloid-beta concentrations can have fungal morphology then I would think that might strengthen your claim and weaken the paper's."

The evidence in the paper consists of a few representative pictures. I have never seen human brain stained for amyloid-beta, but if it stained at all I would bet lots of money that I could find at least one clump with "fungal morphology".

Also, ruling out the other explanations (such as they stained for amyloid) is not the audience's job, it is their job. They are the ones with access to the most detailed information, putting them in the best position to think about various explanations for what could be going on.

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

#148

Post by nonbel »

protomyth wrote: post #85
nonbel wrote: post #82

Earlier quoted context omitted.

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’…

My sarcasm detector is busted, are you for or against control group in this situation?

Perhaps you are basing this on the incorrect premise that Alzheimer's is understood at all. It isn't, and worse essentially no progress has been understanding it for many years. For example, the purpose of APP (amyloid precursor protein) remains mysterious. The same speculations are thrown around now as by the guy who discovered it in the 1980s.

At some point you need to start considering that something is seriously wrong with the research methods or theories. This fungal idea is good to explore, but the evidence provided here is not convincing at all.

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

#149

Post by protomyth »

toast0 wrote: post #143
protomyth wrote: post #142

Earlier quoted context omitted.

Here's my problem, we know the outcome of Alzheimer's, surly we have the data to go ahead without a control group? We've had them before.

Without the control group, you don't know if the change you think you made is the change that made a difference.

Ok, but don't we have a body of knowledge on Alzheimer's that having another control group is redundant? Why do we keep needing new control groups for things that are going to kill people and we know are going to kill people? I cannot get by the ethical problem of knowing we're kill 50% of the people in the study to provide data we already have.

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

#150

Post by dynomight »

dynomight wrote: post #108
dynomight wrote: post #107

Earlier quoted context omitted.

This may be sloppy science, but sometimes discoveries happen in very sloppy and unpredictable ways.

Excuse me. Science only happens in precise and predictable ways.

What I can conclude for sure is that the upvoting/downvoting system is very imprecise, but engaging at the same time.
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