Alzheimer's caused by fungi?
October 16, 2015 4:28 PM   Subscribe

"Our findings provide compelling evidence for the existence of fungal infection in the central nervous system from Alzheimer's disease patients, but not in control individuals." Nature magazine just published a study that claims that Alzheimer's disease is caused by fungi. If this is true, this is amazing and incredibly exciting. (By the way, I've just noticed that our very own cstross was the one who shared it on Twitter.)
posted by Cobalt (66 comments total) 28 users marked this as a favorite
 
Also: horrifying. But it opens up entirely new potential angles to look for a cure from, which is indeed incredibly exciting.
posted by Caduceus at 4:37 PM on October 16, 2015 [5 favorites]


So what does one take to counter a systemic fungal infection? Should I start drinking jock itch ointment?
posted by five fresh fish at 4:39 PM on October 16, 2015 [4 favorites]


Yes.
posted by Wolfdog at 4:42 PM on October 16, 2015 [46 favorites]


Nature magazine just published a study

The study appeared in Scientific Reports, which is published by the Nature Publishing Group, but is a different journal to Nature (Scientific Reports is an open access mega-journal more like PLoS ONE).
posted by James Scott-Brown at 4:44 PM on October 16, 2015 [25 favorites]


So what does one take to counter a systemic fungal infection? Should I start drinking jock itch ointment?

Actually, people do take things like miconazole in tablet form.
posted by clockzero at 4:45 PM on October 16, 2015 [2 favorites]


Should I start drinking jock itch ointment?

I imagine that would prevent you from getting Alzheimer's, but probably not in the way you'd hoped.
posted by Greg_Ace at 4:45 PM on October 16, 2015 [93 favorites]


I wonder how this finding aligns or conflicts with the genetic, or inheritable components of early- and late-onset Alzheimer's Disease?
posted by a lungful of dragon at 4:49 PM on October 16, 2015 [6 favorites]


Should I start drinking jock itch ointment?

May as well be on the safe side, and just eat the whole jock
posted by Greg Nog at 4:51 PM on October 16, 2015 [31 favorites]


This is as important as when they figured out that most stomach ulcers were caused by bacteria... now it's treated with a pill instead of surgery. I hope this works out as well it hints it could.
posted by MikeWarot at 4:51 PM on October 16, 2015 [11 favorites]


If it's true that certain fungi are always present is Alzheimer's patients but not others, it's amazing that we didn't realize it before.

It's possible that this is an error of some kind. I hope there'll soon be many others checking to see if they can replicate these findings.
posted by Sleeper at 4:52 PM on October 16, 2015 [4 favorites]


Important if true. It always amazes me that, even with all our advanced technology and the thousands of man-hours that go into studying major diseases, we can still only guess whether some diseases are caused by a pathogen.

How could this have been missed by previous researchers? Surely the brain tissue of Alzheimer's patients has been examined a billion times before. What did these folks do differently to reveal this hitherto hidden evidence?

If it is a fungus, then there's obviously something about aging that makes people more susceptible to infection.
posted by escape from the potato planet at 4:52 PM on October 16, 2015 [2 favorites]


Life finds a way.
posted by johnnydummkopf at 4:53 PM on October 16, 2015 [7 favorites]


It says they also found fungi in the blood vessels of Alzheimer's patients. How does this happen? Is it a result of the immune system weakening with age?
posted by Kevin Street at 4:56 PM on October 16, 2015 [1 favorite]


Interesting possibility; however, I just want to say as somebody who works for a Alzhiemer's Society that it seems right now that a study comes out every week identifying new contributing factors and possibilities relating to the eitology of the disease, ranging from genetic to lifestyle to environmental factors.

This is a great new avenue for research, and I'm interested to see where it goes, but everything I've learned about the disease in my time there so far is that there is a long history of hope of finding a "silver bullet" for Alzheimer's, with an equally long history of frustration. And in some cases some factors have been announced with great fanfare, only for the further research to show that something about the progression of the disease makes the person more susceptible to retaining the chemical/substance/whatever it is in their brains.

I really hope there's some solid follow-up on this avenue, particularly since treating fungal infections is something we can already do, but I just want to sound the caution alert. I've sat in a lot of rooms over the past few months with families hoping/praying/believing that there's a magic solution out there that will stop or reverse the course of the disease, only to watch the dawning realization that there isn't going to be any magic, and I don't want to see hopes get too high before we have a better understanding of what these findings mean.

(That being said, I really want to buy into this - there are a lot of nasty fungii out there that we know impact behaviour/nervous systems of other animals, so why not? Even if we are only talking a percentage of cases that can be helped by this, it would be a huge step).
posted by nubs at 4:59 PM on October 16, 2015 [87 favorites]


May as well be on the safe side, and just eat the whole jock

Too gamey.
posted by five fresh fish at 5:02 PM on October 16, 2015 [34 favorites]


Do dandruff sufferers get Alzheimer's more than the non-such?
posted by five fresh fish at 5:03 PM on October 16, 2015 [1 favorite]


Twenty-five subjects, no discussion of diagnostic criteria, qualitative methods only, no statistical analysis, no images of the gels or blots (on second look, they're buried in the supplement), no proteomics or mass spec. This is a weak study and may safely be ignored until such time as stronger evidence emerges.
posted by dephlogisticated at 5:06 PM on October 16, 2015 [38 favorites]


Wow. . .if reproduced, this could mean that the news earlier this year about how the immune system is directly connected to the brain could be a huge rung in the ladder of building the science of how it happens.
posted by barchan at 5:08 PM on October 16, 2015


This seems so, so very implausible. I have a very hard time thinking that such a thing would have been missed so far. Nobody saw or identified the fungi on slides? Not one person has ever thought to extract a bit of affected brain tissue and hit it with some general bacterial and fungal primer sets?
posted by Mitrovarr at 5:08 PM on October 16, 2015 [1 favorite]


It's not that implausible. Wasn't a new part of the nervous system discovered earlier this year as well?
posted by I-baLL at 5:11 PM on October 16, 2015 [4 favorites]


I mean seriously running a general fungi primer set on some afflicted brain tissue is a <$100 test a graduate student could do, and running general primer sets on the afflicted tissue would probably be my very first step if I was trying to identify the cause of a disease (but I am a molecular biologist). It's cheap, easy, and obvious.
posted by Mitrovarr at 5:13 PM on October 16, 2015 [3 favorites]


I really, really hope this pans out. There are some familiar doubts: for one thing, almost all of the Alzheimer's patients in the study were 79+, while almost all of the control individuals were well under 79, or even 60. We need a lot more research.

But this is still huge. Fingers crossed.
posted by New Year at 5:14 PM on October 16, 2015 [2 favorites]


Wasn't a new part of the nervous system discovered earlier this year as well?

Not of the nervous system, but the lymphatic system. It was long thought that there were no lymphatic nodes in the top of the skull, closest to the brain. Now they found that there are, they were just always overlooked or destroyed when autopsying heads (I mean, a bone saw does quite a bit of damage, so, you know...).

At least that was my understanding of that news.
posted by daq at 5:16 PM on October 16, 2015 [1 favorite]


They did immunohistochemistry and PCR on tissue from one Alzheimer's disease subject and one control. ONE.
posted by dephlogisticated at 5:24 PM on October 16, 2015 [8 favorites]


Well, even if this doesn't pan out, there's been other exciting research in Alzheimer's disease around amyloid plaques: Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model.
posted by Freen at 5:31 PM on October 16, 2015 [6 favorites]


They did immunohistochemistry and PCR on tissue from one Alzheimer's disease subject and one control. ONE.

To get some idea of the relative difficulty of running PCR on diagnostic samples these days, today I ran six different assays to diagnose the diseases in someone's turf grass.
posted by Mitrovarr at 5:32 PM on October 16, 2015 [28 favorites]


Do dandruff sufferers get Alzheimer's more than the non-such?

The only fungi identified in the paper are Chlamydophila pneumoniae and Candida albicans, neither of which are responsible AFAIK for dandruff. Although I suppose dandruff would be a very mild form of candidiasis.
posted by Nevin at 5:36 PM on October 16, 2015


Isn't dandruff just dead skin cells?
posted by Drinky Die at 5:37 PM on October 16, 2015


Scratch that, they used three AD subjects (and for some reason ten controls) for some of the stains. The Western blot and PCR were one each. I'm not sure I would even call this a pilot study.
posted by dephlogisticated at 5:38 PM on October 16, 2015 [2 favorites]


I'll lay $10 on "didn't properly isolate AD samples from mutual contamination."
posted by gerryblog at 5:41 PM on October 16, 2015 [8 favorites]


I wonder how this finding aligns or conflicts with the genetic, or inheritable components of early- and late-onset Alzheimer's Disease?

I'd be interested in that discussion as well, and this study needs to be replicated with people with early onset AD in addition to just replicated in general. Basically, based on what I know, here's how genetics works with AD:

We talk about AD having two "forms" - familial and sporadic. Familial is where there is a clear family link (at least 2 generations of direct relatives) to what is going on, and it represents something like 2-5% of all cases of Alzheimer's disease. The majority of of AD, then, is what we call sporadic.

Early Onset Familial Alzheimer's Disease (eFAD) and Familial Alzheimer's is straight up genetic; symptoms can start as early as the thirties (early onset is basically dementia starting before age 65). Basically, there are three genes involved - amyloid precusor protien (APP); presenilin-1 (PS-1) and presenilin-2 (PS-2). If you have a parent who has a problem on one of those three genes and you inherit it (a 50-50 proposition), you are pretty much guaranteed to develop Alzheimer's.

Sporadic, on the other hand, has some genes implicated - apolipoprotein E (APOE) is the one I'm most aware of, but I know I've seen some other ones in the literature in the past few weeks (TREM2, CLU, a few others). It has some variable forms. If you have APOE e2, your risk appears to be lower; APOE e4 increases risk somewhat. Most of the population has APOE e3, which doesn't impact your risk either way. But whatever form you have, you still have risk of developing or the potential not to develop AD.

So we tend to talk about modifiable and non-modifiable risk factors when discussing sporadic AD. Non-modifiable factors include your genes, your age (the older you are, the higher your risk), your gender (women are more susceptible then men, in part because of longer life spans), and some other medical conditions such as Parkinson's, MS, kidney disease. Modifiable risk factors include things like not smoking, good cardiovascular health, alcohol use (moderate use - a drink a day - is associated with lowering risk, while heavy use raises risk and outright abstinence also raises risk, but to a smaller degree), level of formal education, and head injuries. So focusing on a healthy diet (like the MIND diet) and exercise, avoiding head trauma (wear your helmets!) and keeping your brain active and engaged are all good things to do. And then there are a whole ton of things being looked at in terms of environment and lifestyle that may or may not play a role in this mix; there just isn't enough data.

This information does seem to tie into some other recent research around the immune system and Alzheimer's. So maybe there's something there. But there's a tremendous amount we don't know yet about the brain and the CNS and how everything might be working together, such as the recent discovery that the lymphatic system connects. We need a lot more information and data, and it might be that despite similarities in symptoms and progression and end result of the disease, the sporadic and familial forms are just the same end points of completely different mechanisms.
posted by nubs at 5:41 PM on October 16, 2015 [20 favorites]


Oh man, the list of fungi they identified in the brains is like an itemized list of common fungi that contaminate DNA reactions in the laboratory.
posted by Mitrovarr at 5:42 PM on October 16, 2015 [37 favorites]


I think they analyzed ten more AD patient samples and ten more controls, after demonstrating the results from patient "AD1" and the initial control. They should definitely access more tissue samples for analysis.

It's interesting. Yeast are known to have their own prions (they have their own system for managing aggregated prions, while we currently have not been able to identify the same sort of system in humans). Is it possible for yeast prions to be introduced into the extracellular matrix, and potentially cause protein misfolding of our own endogenous proteins? Of course, there are also cases of AD related to genetics, and I've seen recent studies that demonstrate the link between good cardiovascular health and a lower rate of Alzheimer's and other forms of dementia.
posted by extramundane at 5:45 PM on October 16, 2015 [1 favorite]


Isn't dandruff just dead skin cells?

Not necessarily. It can be caused by a fungal bloom of Malassezia Globosa which results in seborrheic dermatitis. I have this condition. Changes in the weather combined with diet can tip the balance over to a bloom.
posted by Nevin at 5:55 PM on October 16, 2015 [8 favorites]


The only fungi identified in the paper are Chlamydophila pneumoniae and Candida albicans...

Um, I'm seeing references to C. Glabrata, C. Albicans, C. famata, and P. betae. Chlamydophila pneumoniae and HSV-1 (herpes) are sited as being found in the brain tissue of AD patients, and thought to have some relation to the disease. This paper is trying to determine if a fungal pathogen may be involved, since the cellular damage to the neurons is inconsistent with the kinds of cellular damage that bacteria and virii cause.

Also, as Mitrovarr points out, the list of fungi is basically the list of every type of fungi that you already carry the spores of all the time. I am seriously wondering about their clean-room methodology, and whether they bothered to do a spore collection test on their lab before or after the experiments were performed. They only list their preventative contamination methods with the PCR tests:
A number of measures were used to avoid PCR contamination including the use of separate rooms and glassware supplies for PCR set-up and products, aliquoted reagents, positive-displacement pipettes, aerosol-resistant tips and multiple negative controls.


The part that seems sorta-kinda interesting is that they base this paper on the assumption that systemic fungal infection _could_ explain the progression of the disease, given the way the immune response if ability of the immune system to actually clear a fungal infection is limited in the elderly and immuno-compromised.

What is interesting, and repeatable, however, is the lack of contamination in the Control group. They found extensive fungi in the brain tissue of AD patients. The negative result in the Control group is what needs to be investigated more. Someone smarter than me needs to chime in as to whether that is as relevant as I think it is or not.
posted by daq at 5:56 PM on October 16, 2015 [3 favorites]


Um, I'm seeing references to

I didn't read far enough, obviously!
posted by Nevin at 5:57 PM on October 16, 2015


Scientific Reports is a shit journal.

I've repeatedly tried to unsubscribe from the generic buzzword fueled poorly constructed dross that populates its pages as part of a Nature publishing group journal alert.
posted by lalochezia at 6:01 PM on October 16, 2015 [5 favorites]


I think they analyzed ten more AD patient samples and ten more controls, after demonstrating the results from patient "AD1" and the initial control.

And that's why you don't mash methods and results together. But yeah, it seems like they used one AD patient and one control for the initial stain of several brain regions, then repeated the stain of entorhinal tissue on ten AD patients and ten controls, then stained choroid plexus tissue from a different set of three AD patients. And did the Western and PCR on the initial AD patient and control. What a mess.
posted by dephlogisticated at 6:05 PM on October 16, 2015 [3 favorites]


Isn't dandruff just dead skin cells?

Not necessarily. It can be caused by a fungal bloom of Malassezia Globosa which results in seborrheic dermatitis. I have this condition. Changes in the weather combined with diet can tip the balance over to a bloom.


Seborrheic dermatitis is also more common in people with Parkinson's and other neurological conditions. (Which says nothing about the possible shittiness of this study, of course.)
posted by thetortoise at 6:14 PM on October 16, 2015 [1 favorite]


Seborrheic dermatitis is also more common in people with Parkinson's

But Parkinson's comes first, I think, not the other way around.
posted by Nevin at 6:15 PM on October 16, 2015 [1 favorite]


Fuck those mushrooms. Fuck them right in the gills.
posted by Cool Papa Bell at 6:29 PM on October 16, 2015 [8 favorites]


There's a website for that.
posted by cjorgensen at 6:33 PM on October 16, 2015 [11 favorites]


So those people in The Last of Us were just pensioners? I'm so morally confused!
posted by Pope Guilty at 6:55 PM on October 16, 2015 [2 favorites]


I have thought for a long time, the entanglements they talk about, sounded like mycelium. Since the brain is such a glucose rich environment I wondered if fungal growth in the CNS could effect things, maybe even an endogenous brain drunkeness.

(Uh uh uh, I am not the droid you are looking for.)
posted by Oyéah at 10:02 PM on October 16, 2015


*slowly takes shrooms out of mouth and puts them back in the bag*
posted by Joe Chip at 10:03 PM on October 16, 2015 [6 favorites]


The images in the article don't seem to show any convincing fungal forms. Doesn’t look like any type of fungal infection I’ve ever seen.
posted by Mrjaysoh at 10:04 PM on October 16, 2015


Now all we need is the non-terrestrial connection and we can have BRAIN EATING FUNGUS FROM MARS, as foretold in the National Enquirer.
posted by CheeseDigestsAll at 10:31 PM on October 16, 2015 [2 favorites]


You need to fulfill Koch's postulate (prove causation by infecting a primate) before breaking out the antifungal cream. Otherwise this just means Alzheimer's patients take fewer baths and are more likely to have fungal contaminants in their samples.
posted by benzenedream at 1:49 AM on October 17, 2015 [2 favorites]


As cool/hopeful this sounds, my reaction is tempered by understanding that Alzheimer's is, arguably, poised to explode as the big growth area in medical research. And, as such, we are going to hear these sorts of announcements semi-regulary over the next umpteen years as researchers compete for funding. More power to them, of course, but I'm not going to get too excited, either.
posted by Thorzdad at 5:45 AM on October 17, 2015 [1 favorite]


Did I hear somewhere that smokers get AD less than non smokers? Is nicotine an anti fungal or something?
posted by ian1977 at 6:01 AM on October 17, 2015


May as well be on the safe side, and just eat the whole jock

I'd probably rather have Alzheimer's than BSE, just quietly
posted by flabdablet at 6:42 AM on October 17, 2015


Did I hear somewhere that smokers get AD less than non smokers? Is nicotine an anti fungal or something?

Nicotine binds at nicotinic acetylcholine receptors, which are found in specific pathways in the brain that are strongly affected by Alzheimer's. It's thought that nicotine therefore may compensate somewhat for the effects of Alzheimer's (like boosting a weakened signal), but it doesn't actually slow the neurodegenerative processes of the disease. Several other drugs used for Alzheimer's boost acetylcholine signaling through a different mechanism. Unfortunately, the effect on memory and cognition is fairly small.
posted by dephlogisticated at 6:47 AM on October 17, 2015 [2 favorites]


CheeseDigestsAll: "Now all we need is the non-terrestrial connection and we can have BRAIN EATING FUNGUS FROM MARS, as foretold in the National Enquirer."

And Terence McKenna.
posted by symbioid at 7:22 AM on October 17, 2015 [1 favorite]


I wonder how this finding aligns or conflicts with the genetic, or inheritable components of early- and late-onset Alzheimer's Disease?

I wondered the same, perhaps a genetic predisposition to being susceptible or sensitive to the fungi? If that were the case though you'd expect to find instances of the fungi in non-Alzheimer's patients.
posted by furtive at 7:49 AM on October 17, 2015


So if I strap Pa Ardship into a pair of gravity boots for a few hours each day, will it seep down to his toenails?
(I'll have to tell him that his problem is just that there's a fungus among us. He may not be able to remember where he left his glasses 5 seconds ago, but he still appreciates a dumb joke.)
posted by The Ardship of Cambry at 9:48 AM on October 17, 2015


clockzero: "So what does one take to counter a systemic fungal infection? Should I start drinking jock itch ointment?

Actually, people do take things like miconazole in tablet form.
"

I had to take Diflucan once when I got a yeast infection from my wife (I'm an outie). Glad it worked as her ob/gyn said the only alternative was "the fire stick".

(I still say it sounds like traditional Scandinavian cooking though. "Yeah, I'll take the lutefisk with a side of diflucan.")
posted by Samizdata at 10:15 AM on October 17, 2015 [1 favorite]


I mean seriously running a general fungi primer set on some afflicted brain tissue is a <$100 test a graduate student could do, and running general primer sets on the afflicted tissue would probably be my very first step if I was trying to identify the cause of a disease (but I am a molecular biologist). It's cheap, easy, and obvious.

Is it possible it's so obvious that everyone figured someone else had already tried it?

I feel like if I was working with a bunch of brains, I'd do a suite of blind tests on them to look for patterns. Kind of like the suite of tests that people can do on their blood. Otherwise, how do you ensure you haven't missed something obvious?
posted by mantecol at 11:08 AM on October 17, 2015


mantecol: Is it possible it's so obvious that everyone figured someone else had already tried it?

It's not impossible, but it's really, really unlikely. The most likely possibility is that a bunch of people tried it right around the development of suitable genetic methods, and probably an occasional group does it periodically since then whenever new advances come out. This would also imply that nobody did a next-gen mass sequencing of Alzheimer's patients' brain tissue, looking for organisms that aren't hit by the standard general primer sets and viruses. That seems extremely unlikely as well. Finally, it seems likely to have come up if anyone did an EST library of tissue looking for unusual gene expression patterns, or any similar method.
posted by Mitrovarr at 11:26 AM on October 17, 2015


Otherwise this just means Alzheimer's patients take fewer baths and are more likely to have fungal contaminants in their samples.

And there is certainly a noted problem with Alzheimer's patients and general hygiene; as the disease advances, they are unable to bathe and clean themselves, relying on external caregiving which may not bathe a person as frequently or as thoroughly as they need. In addition, the communication issues also mean that developing injuries and health problems - such as infections - may go unnoticed for some time. For example, bladder infections can be quite common.

Anyways, I reread this again this morning, and the breathless nature of it bugs me more now than it did yesterday, when I was tired and waiting for dinner. It's an interesting avenue for further research, but lines like this: "Proceeding on the assumption that fungi are the aetiological agent of AD, all of the symptoms observed in AD patients can be readily explained" are just way over the top. That's a big assumption for right now; it could be the case, but it could also be the case that the fungi being observed are the result of other changes in the brain that accompany AD making the brain unable to prevent/fight such infections; or there could be other factors that are contributing to cause both AD and fungi. Or it's sample contamination.
posted by nubs at 11:30 AM on October 17, 2015 [3 favorites]


I cannot stress this enough; if you are ever working on a fungal sequencing project, and the result is 'Malassezzia, Candida, and Saccharomyces', the proper response is not 'publish a paper', it's 'dump your reagents and bleach the lab'. Oh, and I missed this before, but Neosartorya is just the sexual state of Aspergillus. The only box on the common laboratory contaminant checklist they are still missing is Pichia.

The collection of fungi listed is also biologically implausible. There are ascomycetes and basidiomycetes, some of which are primarily yeast-like, and others which are mold-like. Some are animal-associated, some are environmental saprobes, some are common plant pathogens. There is basically nothing holding them together as a group except that they're all members of common genera.
posted by Mitrovarr at 11:41 AM on October 17, 2015 [19 favorites]


So if the elderly smell moldy, they might actually BE moldy!?
posted by Muncle at 12:34 PM on October 17, 2015 [1 favorite]


This is basically the plot of The Girl With All The Gifts, but with Alzheimers instead of zombies.
posted by Joe in Australia at 2:51 PM on October 17, 2015


Metafilter: just eat the whole jock.

This article is particularly relevant to me this morning, since I just learned last night that a close family member has Alzheimers. The article has issues - for example their control group skews significantly younger than the patients - but it was an interesting and thought-provoking read.
posted by Autumn Leaf at 2:53 PM on October 17, 2015


...with Alzheimers instead of zombies.

If the TV / movie / novel people run with that, it's going to be a depressing decade or two.
posted by Wolfdog at 3:57 PM on October 17, 2015


Onychomycosis is fungus of the toenail and it has one treatment with 6-9% cure and 10-50% recurrence. (Wikipedia) Fungus is a tough fight.
posted by xtian at 7:21 PM on October 17, 2015 [1 favorite]


Just 20 people total in the analysis but 100% results in the 10 that showed fungal infection. Could be a big deal.
posted by uwreed at 11:45 AM on October 18, 2015


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