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

A.B.

Senior Member
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3,780
The possibility that Alzheimer’s disease (AD) has a microbial aetiology has been proposed by several researchers. Here, we provide evidence that tissue from the central nervous system (CNS) of AD patients contain fungal cells and hyphae. Fungal material can be detected both intra- and extracellularly using specific antibodies against several fungi. Different brain regions including external frontal cortex, cerebellar hemisphere, entorhinal cortex/hippocampus and choroid plexus contain fungal material, which is absent in brain tissue from control individuals. Analysis of brain sections from ten additional AD patients reveals that all are infected with fungi. Fungal infection is also observed in blood vessels, which may explain the vascular pathology frequently detected in AD patients. Sequencing of fungal DNA extracted from frozen CNS samples identifies several fungal species. Collectively, our findings provide compelling evidence for the existence of fungal infection in the CNS from AD patients, but not in control individuals.

http://www.nature.com/articles/srep15015
 
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Marky90

Science breeds knowledge, opinion breeds ignorance
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1,253
Wow. Freaky. Could it be the trigger? How in the world does the fungi get into the brain without the immune system attacking it?
 

A.B.

Senior Member
Messages
3,780
Wow. Freaky. Could it be the trigger? How in the world does the fungi get into the brain without the immune system attacking it?

This could be the holy grail of AD research, and also be relevant for other diseases such as a subset of ME/CFS. There is so much interesting information in this article. There is increased immune system activity and inflammation in AD, so the immune system is reacting to something. The amyloid accumulation might be the result of the ongoing battle:

Αβ peptide exhibits antimicrobial activity and shows particularly strong inhibitory activity against Candida albicans27.

Proceeding on the assumption that fungi are the aetiological agent of AD, all of the symptoms observed in AD patients can be readily explained. For example, the slow progression of the disease fits well with the chronic nature of fungal infections if they remain untreated. Moreover, inflammation and activation of the immune system may be due to an infectious fungal agent. Disseminated fungal infections can induce cytokine production53,54,55, which can take place years before the onset of cognitive decline as observed in AD. Thus, this disseminated infection may slowly spread to the CNS and synaptic dysfunction and neuronal loss takes place only when the fungal burden in some areas of the CNS is high. It is quite possible that the existence of one fungal infection may facilitate the colonisation by other fungal species that can affect other areas of the CNS, giving rise to mixed fungal infections. The diversity of fungal species that can affect the CNS, as well as the combinations of these species, may account for the observed differences in the evolution and severity of clinical symptoms found in AD patients. The pathology of the blood vessels observed in most AD patients can also be explained since they can be infected by fungi37,38,39, particularly arteries, where the oxygen content is higher. Finally, the genetic predisposition observed in approximately 2–5% of AD patients can simply be due to their predisposition to acquire fungal infections because the genetic background of each individual is permissive for this56,57. To the best of our knowledge, none of the symptoms established in AD pathology seem incompatible with the concept that AD may be caused by fungi. Moreover, the dissapointing results obtained in human clinical trials designed to lower the burden of β-peptide or tau tangles does not support the amyloid cascade hypothesis12,13,14. These findings suggest that the main pathological agent in AD is still unidentified.
 
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Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
This could be the holy grail of AD research, and also be relevant for other diseases such as a subset of ME/CFS. There is so much interesting information in this article. There is increased immune system activity and inflammation in AD, so the immune system is reacting to something. The amyloid accumulation might be the result of the ongoing battle:

I agree, the fact that everybody with AD had it certainly begs for a larger study..

Take a look at this @Jonathan Edwards, do you think its possible that fungi could be relevant in a subset of ME-patients as A.B proposes?
 

A.B.

Senior Member
Messages
3,780
I agree, the fact that everybody with AD had it certainly begs for a larger study..

Take a look at this @Jonathan Edwards, do you think its possible that fungi could be relevant in a subset of ME-patients as A.B proposes?

If this is confirmed to be a real finding then I'd definitely want some researchers to look at ME/CFS with the same techniques. Dr Lipkin has expressed interest in exploring the fungal infection hypothesis in the past, so we already have at least one interested researcher.
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
If this is confirmed to be a real finding then I'd definitely want some researchers to look at ME/CFS with the same techniques. Dr Lipkin has expressed interest in exploring the fungal infection hypothesis in the past, so we already have at least one interested researcher.

Indeed.

I lived in a fungus infected room 2 years prior to getting sick..Could be relevant..
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
I first heard rumors of this kind of thing in the 90s. Nothing came of it. If they finally have the evidence this could lead to a huge leap in our understanding of both AD and other diseases. It could also lead to treatments.

However we have to be careful that this is association not causation. It might be causal, or it might be because of immune problems, either in AD itself or as a root cause of both AD and the fungal infection.

I think this is very relevant to ME and CFS research, and possibly other related diseases.
 

A.B.

Senior Member
Messages
3,780
If fungal infection were at the heart of ME/CFS, how would the apparent success of killing off b cells vis-a-vis Rituximab play into this?

A fungal infection affecting blood vessels (one of the findings in the study) might resemble an autoimmune condition that also affects blood vessels, which is the current hypothesis on CFS by Fluge and Mella. The patients that show a good response to Rituximab probably don't have any significant infections. Patients that don't respond could have an entirely different problem.


PS: Baraniuk's CFS proteome study says: the proteome was remarkable for the number of proteins associated with protein misfolding and cerebrovascular amyloidosis syndromes.
 
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Jonathan Edwards

"Gibberish"
Messages
5,256
I agree, the fact that everybody with AD had it certainly begs for a larger study..

Take a look at this @Jonathan Edwards, do you think its possible that fungi could be relevant in a subset of ME-patients as A.B proposes?

I think we should keep an eye on Googling for candida and Alzheimer's for a week or two. My initial reaction is that these findings are unlikely to be real. Fungal elements often turn up in tissue sections - they get there during the tissue preparation. But the fact that this group has felt the findings are worth publishing suggests that there might be more to it than that. If it is real then there will be a splash of debate and other groups will try to replicate the findings.

Candida living in this way in brain without any inflammatory response would be weird - since yeasts are potent stimuli of innate inflammatory pathways like complement. Generally speaking once a fungus has managed to survive in internal tissue for more than a matter of hours or days it spreads and takes over and kills the patient within months if not weeks. There are some extremely slowly progressing fungi like Madurella grisei but there is an advancing front of fungal growth to see.
 

A.B.

Senior Member
Messages
3,780
My initial reaction is that these findings are unlikely to be real. Fungal elements often turn up in tissue sections - they get there during the tissue preparation.

They say that fungus was found inside cells and even the cell nucleus. That seems hard to explain by accidental contamination.

Elsewhere, the study has been criticized for not demonstrating that the antibodies don't bind to amyloid. Since they're using polyclonal antibodies they don't know what they're really staining.
 

Jonathan Edwards

"Gibberish"
Messages
5,256
They say that fungus was found inside cells and even the cell nucleus. That seems hard to explain by accidental contamination.

Elsewhere, the study has been criticized for not demonstrating that the antibodies don't bind to amyloid. Since they're using polyclonal antibodies they don't know what they're really staining.

The staining does not look morphologically like an amyloid pattern so I would discount that I think. At least some of the pictures look like micro-organism components. I think you can probably get contamination looking as if it is just about anywhere - particularly if these are cryostat sections. Once the tissue is cut, yeast can land wherever. I cannot see enough from the micrographs presented to get an idea of what is happening. I think I could tell from the original micrographs.

Where as the study been criticised? I would be interested to know what the feedback is.
 

wastwater

Senior Member
Messages
1,271
Location
uk
I had a meningitis scare when younger,I wonder if it might of had something to do with cryptococcus