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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

#131

Post by jschwartzi »

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 interesting.

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

#132

Post by epalmer »

thanatosmin wrote: post #75

As a biomedical researcher, I'm confident in calling this sloppy science. There is no quantitation of staining differences across multiple fields (to demonstrate that the images aren't hand picked), no controls with the PCR study (or even showing the results besides one in the supplement), and no demonstration that the antibodies don't bind to amyloid. Extraordinary claims require extraordinary evidence, and this wou…

I'm not a scientist and defer to your judgement as to the quality of the research method. But if there is even a remote possibility of AD being caused by or someway associated with Fungus infections than I would hope someone does follow up research that is rock solid and not sloppy.

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

#133

Post by tankenmate »

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?

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

#134

Post by nextos »

pcwalton wrote: post #81
thanatosmin wrote: post #75

As a biomedical researcher, I'm confident in calling this sloppy science. There is no quantitation of staining differences across multiple fields (to demonstrate that the images aren't hand picked), no controls with the PCR study (or even showing the results besides one in the supplement), and no demonstration that the antibodies don't bind to amyloid. Extraordinary claims require extraordinary evidence, and this wou…

I'm curious: how does something this obviously flawed get through peer review for Nature? (I believe you that this is bad science.) Edit: I answered my own question here: https://en.m.wikipedia.org/wiki/Scientific_Reports (Summary: It's not Nature; it's a "megajournal" affiliated with it with apparently much lower editorial standards.)

Exactly. Scientific Reports (and Nature Communications) is sometimes used for papers that don't get into Nature or any of its siblings (Genetics, Methods, Protocols, Biotechnology).

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

#135

Post by adrianN »

nextos wrote: post #134
pcwalton wrote: post #81

Earlier quoted context omitted.

I'm curious: how does something this obviously flawed get through peer review for Nature? (I believe you that this is bad science.) Edit: I answered my own question here: https://en.m.wikipedia.org/wiki/Scientific_Reports (Summary: It's not Nature; it's a "megajournal" affiliated with it with apparently much lower editorial standards.)

Exactly. Scientific Reports (and Nature Communications) is sometimes used for papers that don't get into Nature or any of its siblings (Genetics, Methods, Protocols, Biotechnology).

Can confirm. Had a paper rejected by Nature with the suggestion to send it to Scientific Reports instead. Scientific Reports accepted it.

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

#136

Post by kaitai »

et2o wrote: post #51
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).

Most doctors are constantly learning new information. It's not just refresher courses, you have to pass frequent and comprehensive examinations to stay board-certified. I have no idea why HN has this bias against physicians.

Frequent = a test every ten years in internal medicine and some continuing education/maintenance of certification. Even that is under attack (http://knowledgeplus.nejm.org/abim-moc-petition-reveals-deba...).

Doctors are human and some are constantly learning new information while others aren't. There are a lot of pressures on them that are perhaps orthogonal to "learning new things" and "keeping up with the best evidence."

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

#137

Post by [deleted] »

TeMPOraL wrote: post #104
nonbel wrote: post #83

Nature is not a good scientific journal. The good info will be found in highly specialized journals. The amount of BS in scientific journals is related to prestige like this: x=seq(0,1,by=.01); plot(x,dbeta(x,.5,.5), xlab="Prestige", ylab="BS")

For those without a R interpreter handy, Emacs to the rescue: ^ | | | | | | | | | | | | | \ / | | | | \ / | | | | \ / | \ / | \ / B | \ / S | \ / | -\ /- | \ / | -\ /- | -\ /- | --\ /-- | --\ /-- | ---\ /--- | -----\ /----- | ----------------- | +---------------------------------------------------------------------------------> Prestige (Also an on-line R interpreter: http://www.r-fiddle.org/. )

[deleted]

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

#138

Post by toast0 »

protomyth wrote: post #126
zaroth wrote: post #92

Earlier quoted context omitted.

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 agreei…

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 probably depend on the side effects of the anti-fungal. Another less invasive way would be to test for fungal presence in groups with and without the disease, likely through autopsies, since sampling a live brain seems intrusive.

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

#139

Post by Geeek »

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

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

#140

Post by TeMPOraL »

sooheon wrote: post #113
TeMPOraL wrote: post #104

Earlier quoted context omitted.

For those without a R interpreter handy, Emacs to the rescue: ^ | | | | | | | | | | | | | \ / | | | | \ / | | | | \ / | \ / | \ / B | \ / S | \ / | -\ /- | \ / | -\ /- | -\ /- | --\ /-- | --\ /-- | ---\ /--- | -----\ /----- | ----------------- | +---------------------------------------------------------------------------------> Prestige (Also an on-line R interpreter: http://www.r-fiddle.org/. )

What package(s) did you use to create this?

I used http://r-fiddle.org to verify what was the intended function, then used built-in Artist Mode (M-x artist-mode) to draw an ellipse for function and square for axes, and finally cut it down in fundamental-mode and added labels. It's basically vanilla Emacs, but I admit to using multiple-cursors.el for some cleanup. It's an excellent addon mode offering a more interactive way to do some things you'd otherwise do via keyboard macros. Check out [0] and [1].

[0] - https://github.com/magnars/multiple-cursors.el

[1] - http://emacsrocks.com/e13.html

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