Alzheimer's might be transmissible in similar way as infectious prion diseases: study

reply to post by DevolutionEvolvd

Originally posted by DevolutionEvolvd

Reference? ...Just curious.

www.liebertonline.com...

Thanks. ...You do realize the focus on rejuvenation and longevity products clearly indicates a conflict-of-interest, and most likely an narrow focus -right?

Prions are infectious - they're "proteinaceous infectious particles" that infect other proteins of a similar structure - and they do disrupt metabolism.

Not necessarily. There are infectious and non-infectious prions.

Hmmm. According to the language police, there are infectious prions (infectious misfolded proteins) that infect the "prion protein" to cause prions diseases (TSE's), and there are other infectious misfolded proteins that cause "proteinopathies," "misfolded protein diseases" or "conformational disorders.

They're all infectious - the current question is whether or not they're "transmissible." ....all you really need to do is research a bit more, and do a little thinking to answer that question.

And there's a clear difference.

Really? Care to explain?

But...in any case, I was using the term in a sense of person-to-person transmission. And that just because both are obviously progressive, or infectious endogenously, it doesn't mean that both are transmissible exogenously.

Think about it.

Having seen the effects of Alzheimer’s Disease first hand, on the person and their family, there are a few things that can be stated:

Here is a brief history of Alzheimer’s disease: In the early 1900’s a physician named Alois Alzheimer provided care for a patient with rapidly declining severe dementia. After she died, he was able to perform an autopsy on her brain. Advances had recently been made in histology and microscopy, so Alzheimer was able to study, in detail, the cellular changes in the brain’s nervous tissue. What he found was an atrophy of the gray matter surrounding the brain. He also found bundles of neurofibers and the plaques that are now a distinguishing characteristic for a definitive diagnosis of what we call Alzheimer’s Disease today.


Since World War II, the number of people afflicted with this disease has tripled, and ultimately is the number 6 cause of death in the United States of America. The estimates of those who could be potentially affected is staggering so research in this area has become very crucial, as the number of qualified care facilities are few and the reality is that this is going to get far worse before it gets better, a silver tsunami is about to hit, and most countries are neither prepared or ready for this to happen.

There are too many questions about this disease, and the race is on to find a cure or even a means to help those who are either at risk or are affected by it. The scientists and researchers do not know how such happens. I should know, as my own mother is affected with this disease, and her downward spiral is faster than we anticipated, and the ultimate sad portion, is that she like so many who are like her, do not even realize that they are sick. And ultimately it is far worse on the caregivers, who give tirelessly day after day, year after year to care for those who are afflicted with this disease, with what would appear to be very little hope or relief.

If this is an infectious disease, the question is how is it spread and ultimately how far has this spread, along with how many of us are at risk for getting such? Those are ultimately the questions that must also be answered, and like all diseases, that have no cure, that appear with out warning, are too numerous with too few answers coming forth. And like all diseases that are progressive, time is not a luxury that we have.

reply to post by Matt1951


Interestingly enough, coffee consumption is also correlated with decreased risk of developing diabetes.

Originally posted by soficrow

Thanks.

...You do realize the focus on rejuvenation and longevity products clearly indicates a conflict-of-interest, and most likely an narrow focus -right?

Absolutely, Sofi! That's just something I found, honestly. I've heard from multiple sources, and read in journal articles, that AGEs have a tendency to misfold proteins.

They're all infectious - the current question is whether or not they're "transmissible." ....all you really need to do is research a bit more, and do a little thinking to answer that question.

Now, you know how much I respect your knowledge on this subject, as I've told you many times. This is something I've always wanted to dig into a little bit deeper...but I never have the drive to spend hours researching the data. And it mainly stems from an associative bias, of sorts. I can honestly tell you that a few researchers and doctors in the field of biochemistry and nutrition have swayed my opinion on prion diseases and their connection to degenerative, chronic diseases. It's bad, I know. I am biased, but I DO want to see the data for myself and make the connections, or lack thereof, to settle my insatiably curious mind.

...because I do see an alarming trend that even my biased brain can't ignore. That is that there are too many correlations that can't simply be dismissed as circumstantial associations.

I will say, however, that I see a unsurprising amount of ambiguity in this field of research. I say unsurprising because it runs rampant in nutrition research, which is my main area of focus.

And there's a clear difference.

Really? Care to explain?

www.sciencedaily.com...

he research team took on the prion-forming domain of the fungal protein HET-s. At a pH value of 7—under physiological conditions—this domain forms infectious fibrils. In acidic solution, at pH 3, it also forms fibrils, but these are not infectious.
By using nuclear magnetic resonance spectroscopy (NMR), the team was able to get a closer look at this protein. NMR allows for the evaluation of interactions of the nuclear spins of specific atomic nuclei with each other and their chemical surroundings, which gives information about the structure and dynamics of molecules and molecular fragments.
Here’s what the researchers found: The spectra of the pH 7 and pH 3 versions of the prion differ significantly. Both are mainly arranged in the rigid β-sheet structure, but up close the structures diverge widely. Particularly striking is the fact that the infectious pH 7 form has highly flexible loops in addition to the rigid domains. These are absent from the non-infectious pH 3 prions.
“The lack of infectiousness of the pH 3 fibrils is thus related to the fact that their molecular structure is significantly different from that of the fibrils formed at physiological pH,” the researchers conclude.

Think about it.

But, Sofi, cancer is characteristic of "infectious" endogenously. It's almost virulent in the body...especially when it because metastatic. But is cancer transmissible? (I have a feeling you're going to say yes....)

reply to post by DevolutionEvolvd


If you'll pardon the brief insertion... I believe that since cancerous tumor formation can be the result of viral activity, it is clear that at least logically, it can be transmissible. The question is how much so, and are their elements of the environment, such as it is, that contribute to the propagation of the causes?

If not, can a cure be identified for each causative factor; and if so, how do we identify and control those environmental factors.... and more cynically, if we could... would profit stand in the way?

I live with my grandfather who has Alzheimers, he is 78, what is this study trying to tell me?

Originally posted by Maxmars
reply to post by DevolutionEvolvd

 

If you'll pardon the brief insertion... I believe that since cancerous tumor formation can be the result of viral activity, it is clear that at least logically, it can be transmissible.

Right...Human Papalomavirus (HPV) can indeed cause cancer, so I see what you're saying.

The question is how much so, and are their elements of the environment, such as it is, that contribute to the propagation of the causes. If not, can a cure be identified for each causative factor; and if so, how do we identify and control those environmental factors.... and more cynically, if we could... would profit stand in the way?

If you're talking of Alzheimers, then yes. Those elements in the environment, at least those which probably have the greater effect on disease development, would undoubtedly be dietary. For instance, eat foods that promote and develop diabetes and insulin resistance will lead to high blood sugar. Hyperglycemia increases glycation of proteins and Advanced Glycated End products...which contribute heavily to the formation of amyloid plaques, and even possibly Prions. And high fructose consumption increases fructose in the blood, which are 10 times more likely to bind to proteins and glycate.

So...the answer, Max, would be that it can be controlled, and prevented, through our dietary habits. There's been a lot of research lately showing a huge correlation between diabetes and Alzheimer's incidence. So much so that some researchers are calling Alzheimer's Type 3 Diabetes.

reply to post by DevolutionEvolvd

...You do realize the focus on rejuvenation and longevity products clearly indicates a conflict-of-interest, and most likely an narrow focus -right?

…I've heard from multiple sources, and read in journal articles, that AGEs have a tendency to misfold proteins.

Just as many sources, researchers and journals report the opposite - prions create AGE's. For example,

…The glycation of prion protein to form advanced glycation end-products (AGE) interacting with specific receptors placed on neighboring cells (RAGE) represents the key hypothesis to be discussed.

PMID: 21814041

The thing to remember is that nothing has been found to target prions directly - so everyone and their dog is out looking for a point on the pathway or cascade that might be disrupted to stop the disease process - hence the hope, and focus on AGE's by your "Rejuvenation Researchers" in Dusseldorf.

My concern is that the corporate focus on blaming the victims while hawking snake oil is more than catastrophic.

Disregarding the evidence that prions are a mechanism in the evolutionary process, serves to dismiss the rationale for environmental responsibility.

They're all infectious - the current question is whether or not they're "transmissible." ....all you really need to do is research a bit more, and do a little thinking to answer that question.

I see a unsurprising amount of ambiguity in this field of research.

As evidence of ambiguity you quote a ScienceDaily article with a really bad headline, and leave out some rather definitive information. I've pulled a few different bits to help you better understand the issue (which clearly the headline writer did not).

Briefly, what the article is saying is that, yes, environmental changes can cause proteins to misfold; sometimes the misfolded proteins are infectious and propagate; sometimes the misfolded proteins are not infectious and do not propagate. Of note: infectious misfolded proteins can be called prions, while non-infectious ones are not prions and should not be called by that name (it's self-contradictory). …The way to tell the difference between infectious and non-infectious proteins is to watch and see if they spread; if they spread, they're infectious.

…Granted, TPTB pulled a fast one when they decided to name a particular normal protein the "prion protein" - thus guaranteeing muddy waters, confusion and misunderstandings.

Why are some proteins infectious while others are not?

….The word prion is derived from the term Proteinaceous Infectious Particle.

The research team took on the prion-forming domain of the fungal protein HET-s. At a pH value of 7—under physiological conditions—this domain forms infectious fibrils. In acidic solution, at pH 3, it also forms fibrils, but these are not infectious.

**

ABSTRACT for the ORIGINAL RESEARCH ARTICLE:
Infectious and Noninfectious Amyloids of the HET-s(218–289) Prion Have Different NMR Spectra

The molecular basis for prion infectivity is not yet understood. The NMR spectra of noninfectious and infectious amyloids of the prion-forming domain 218–289 of the fungal prion HET-s are clearly different (see picture) but are indicative for a cross-β arrangement in both cases. The fibrils formed at pH 3 are not infectious because their molecular structure apparently differs substantially from that formed at physiological pH.

reply to post by DevolutionEvolvd


......continued.......

DevolutionEvolvd
...cancer is characteristic of "infectious" endogenously. It's almost virulent in the body...especially when it because metastatic. But is cancer transmissible? (I have a feeling you're going to say yes....)

Maxmars
…since cancerous tumor formation can be the result of viral activity, it is clear that at least logically, it can be transmissible. The question is how much so, and are their elements of the environment, such as it is, that contribute to the propagation of the causes?

If not, can a cure be identified for each causative factor; and if so, how do we identify and control those environmental factors.... and more cynically, if we could... would profit stand in the way?

…..the answer, Max, would be that it can be controlled, and prevented, through our dietary habits.
….Alzheimers, then yes. Those elements in the environment, at least those which probably have the greater effect on disease development, would undoubtedly be dietary.
…it can be controlled, and prevented, through our dietary habits.

Again with the corporate legal defense - deny culpability, blame the victims, deny liability.

I do think individuals have some power over their own health - but NOBODY lives in absolute isolation, untouched by common environmental contaminants - and there's a HUGE difference between individual empowerment and blaming the victims outright. Shame.

And again - the corporate focus on blaming the victims while hawking snake oil is more than catastrophic.

Disregarding the evidence that prions are a mechanism in the evolutionary process just dismisses the need for environmental responsibility.

But for discussion purposes, can you please clarify? Are you saying a) it's what we eat that creates prions, or b) what we eat creates the internal conditions that create prions? Are you also saying c) nothing else in the external environment might cause prion diseases in humans, and d) prions are not infectious or transmissible?

…Also, can you please comment on your understanding of the notion that prions are a) sporadic, b) familial, and c) acquired?

reply to post by soficrow


Well, glycation occurs when a fructose or glucose molecule binds with a protein....any protein, whether it's misfolded or not. Prions aren't making/creating AGEs. Although it's not typically at the forefront of discussion, it is a biochemical fact that Glycation propegates the formation of misfolded proteins. They're not getting backwards, Sofi.

And prions aren't causing Advanced Glycation End-products. When too much fructose is consumed, it makes its way into the bloodstream because of an overload in the liver. Fructose has a high propensity to glycate...and when there's a lot in the bloodstream, the binding of fructose to a protein or lipid is almost inevitable. It doesn't matter if the protein is misfolded or not.

reply to post by RelentlessLurker


aluminum doesn't cause Alzheimer's....research it.

Also could the evidence of prions relate to a genetic defect within that cell might be a symptom of some kind of enviromental contamination from manmade chemicals. It seems that we have been playing Gawd with Mother Nature for years and I am sure there are many mistakes or unintended results. I know that there have been many different Madcow infected animals so it has to be transmissionable. The real question how this disease hits the body

My grandmother died of an altimzers related injury. I must say it was sad watching her go down hill and how her personality changed. I remember at one point she could not even remember what toliet paper was for. However, you learn things that were never mentioned before like; How she ended up with a shotgun wedding! And that she was "expecting" after meeting my grandfather for the first time. She recalled all of the details with clarity saying she was with her girl friend, Edna, at a small store in Hametown (near Dallastown, PA) and she saw my grandfather , Spencer, at the store with one of his friends. While her friend wanted to get busy with grandads friend. And since grandad had a car they went fro a ride...then she skips over to saying, "I was only with him that one time." Anyway I had known that my great grandmother brought Spencer down and made him get married. From what was said he didn't want too but his mother put her foot down! When my dad retired the social security said it was not his last name on the orginal birth certificate but my grandmother maiden name.

Originally posted by soficrow

But for discussion purposes, can you please clarify? Are you saying a) it's what we eat that creates prions, or b) what we eat creates the internal conditions that create prions? Are you also saying c) nothing else in the external environment might cause prion diseases in humans, and d) prions are not infectious or transmissible?

Well, seeing that what we eat directly affects the amount of Glycation and creation of AGEs, then...yes. If we're consuming a diet that promotes Glycation, it will also promote the misfolding of proteins and accelerate the process. So...I guess the answer is B! I am by no means, however, saying that prion diseases aren't transmissible or that prions only originate endogenously in humans.

Perhaps the confusion stems from my adherence to the context...speaking of Alzheimer's.

…Also, can you please comment on your understanding of the notion that prions are a) sporadic, b) familial, and c) acquired?

Sure. Sporadic, which is probably the type that is caused by conditions in which damage leads to misfolding (much like damage leads to mitochondrial damage and eventually mutations and...cancer) or environmental factors such as diet which create an environment in which protein misfolding becomes accelerated.

Familial...of course is genetic. But genetic mutations as such are rare (as far as we know?) Genetics isn't my thing...

And...Acquired would undoubtedly be attributed to the ingestion of animal meats infected with prion disease...causing CJD.

Is that what you were looking for? I know it's basic understanding, so don't scold me!

reply to post by soficrow


Sofi, What are your diet recommendations in light of this information? I know this is not official medical advice, but I respect your opinion on the matter. Do you think meat should be cut out entirely, or just mass produced beef? Also, are there any natural remedies or buffers we can use to slow/thwart these toxins?

This applies to anyone else as well. If there are any dietary suggestions for protection against protein misfolding I'd like to hear them. I know someone earlier in the thread mentioned coffee. I'm going to try to cut out sugar, but I can still try my coffee black.

Sorta kinda ot, but not, but this sounds sorta like what john titor was talking about- about how in the future they find out that the food was not as safe as thought and diseases like CJ become rampant.

reply to post by DevolutionEvolvd

A HUGE range of external environmental changes and exposures can cause proteins to misfold and become infectious. For example…

Numerous now-common medical drugs contain infectious misfolded proteins. And are implicated in Alzheimer's. Also, such drugs and their infectious misfolded proteins cause immunogenicity, affect the immune system, and trigger auto-immune responses. Diabetes is one of the many new diseases with an auto-immune component that may be caused by the infectious misfolded proteins in medications.

Obviously, Big Pharma, like agribusiness, would much rather "blame the victims" than take corporate-personal responsibility. And they are quite able to exploit "New Age" pseudo-medicos - and maneuver them into fueling their Denial Machine, creating a false "debate" and manipulating public perception.

A Role for Protein Misfolding in Immunogenicity of Biopharmaceuticals

…..misfolding of therapeutic proteins is an immunogenic signal and a risk factor for immunogenicity. ……Over the past decades, the use of therapeutic proteins has become common practice in medicine ……

Protein misfolding is an intrinsic and problematic property of proteins, which underlies a variety of degenerative diseases, such as Alzheimer disease. These diseases are characterized by the occurrence of fibrillar deposits, classically termed amyloid, containing aggregates of misfolded proteins.

……experiments pointed out that biopharmaceuticals, like any other protein, are amyloidogenic and that misfolding, detected by amyloid markers, takes place in several preparations. These markers, however, are not necessarily specific for fibrillar amyloid, but also for smaller misfolded protein species.

….. Various Biopharmaceuticals Display Amyloid-like Properties upon Exposure to Conditions of Stress, Indicating Protein Misfolding — During manufacturing and storage, biopharmaceuticals may also become exposed to various conditions of stress that can potentially underlie protein misfolding and the formation of amyloid-like properties.

…….Our results point to a common mechanism by which the immune system perceives misfolded proteins. We hypothesize that this lies in the changed conformation of the protein backbone itself. This implies that the innate immune system may be activated by recognition of the amyloid-like properties of misfolded protein. …

True, food processing and manufacturing creates infectious misfolded proteins, aka prions - not just drug manufacturing. But it's a far cry from acknowledging that fact to blaming the victims for eating the diet imposed on them by the food industry.

Well, glycation occurs when a fructose or glucose molecule binds with a protein....

Glycation usually refers to the "uncontrolled, non-enzymatic reaction of sugars with proteins."

But - the prion protein (PrPc) already IS a glycoprotein in its normal form. Before its transition to PRP(Sc). Meaning that it starts out as a sugar-protein "hybrid." ….The "glycation" that occurs during misfolding is genetically coded - the (infectious) misfolding does NOT change the chemical composition of the protein, just its shape.

A hallmark of prion diseases in humans and animals is the conversion of the cellular prion protein PrPc to a pathogenic isoform, denoted PrPSc. …..All available data indicate that the only difference between PrPc and PrPSc resides in their conformation, emphasizing a critical role of protein folding in the pathogenesis of prion diseases.

Prions aren't making/creating AGEs. …it is a biochemical fact that Glycation propegates the formation of misfolded proteins.

Where are your references proving this "biochemical fact"?

Remember - association doesn't prove causation; a role in facilitating prion propagation and accelerating disease progression does not mean AGE's create prions - just that they help them.


..........continued next post..........

.....continued from above.......

…..And prions aren't causing Advanced Glycation End-products. ……When too much fructose is consumed, it makes its way into the bloodstream because of an overload in the liver. Fructose has a high propensity to glycate...and when there's a lot in the bloodstream, the binding of fructose to a protein or lipid is almost inevitable. It doesn't matter if the protein is misfolded or not.

….Again - the normal prion protein already is a glycoprotein - when it misfolds, the chemistry does not change, only the shape or "conformation."

Moreover, research identifies the receptor for AGE's - not the AGE's themselves - involved with the already misfolded amyloid-like protein in the disease process.

…..several cellular receptors for the amyloid-like protein fold have been identified: scavenger receptor A, CD36, receptor for advanced glycation end products, low density lipoprotein receptor-like protein, and scavenger receptor B type I (17). Moreover, these receptors are expressed on dendritic cells and could initiate an immune response against these proteins (34, 38).

The question remains - what causes the proteins to misfold in the first place?

The answer is - a HUGE range of environmental changes and exposures can cause proteins to misfold and become infectious. Some misfolding happens internally, due to exposures "chosen freely" by the individual, and AGE's might prove to be a cause of certain proteins' misfolding.

But the vast majority of infectious misfolded proteins in our world are created externally, and result from industrial processes and activities like drug manufacturing and food processing.

reply to post by blargg

Originally posted by blargg
reply to post by soficrow

 

Sofi, What are your diet recommendations in light of this information? I know this is not official medical advice, but I respect your opinion on the matter. Do you think meat should be cut out entirely, or just mass produced beef? Also, are there any natural remedies or buffers we can use to slow/thwart these toxins?

You're right - I am NOT offering medical advice, but here's what I know.

First off, please, please think of prions as an evolutionary process - they confer benefits, even if we don't yet know what they are. ....At the very least, they help our bodies adjust and adapt to the crap in our world.

DO try to minimize your exposures. Eat real food that's NOT processed - and aim for a balanced diet with lots of nutrients. I eat mass-produced beef, not frequently, because I can't afford pseudo-organic and I don't think anything is uncontaminated anymore. ...I do know that prions of different strains seem to compete with one another, so variety is key - the more different prions there are in your body, the better off you are.

...Beyond that, focus on inhibiting propagation

The best prion therapeutics are still natural - green tea; curcumin from curry, cumin or turmeric; sage; and (unnatural) antihistamines and statins. [Note: Statins cause killer fibromyalgia in me - I won't take them. I do take benadryl and ranitidine, but they're not on the list.]

New Inhibitors of Scrapie-Associated Prion Protein Formation in a Library of 2,000 Drugs and Natural Products

Several classes of compounds were represented in the 17 most potent inhibitors, including naturally occurring polyphenols (e.g., tannic acid and tea extracts), phenothiazines, antihistamines, statins, and antimalarial compounds. ...many are either approved human drugs or edible natural products...

Also - inflammation and oxidation help prions propagate. Go with anti-inflammatories whenever you can - like cinnamon, aspirin. Same with antioxidants - Vitamin C is king.

.....And try not to stress about it - stress is a killer, and actually can create prions. Really.

imho - the most realistic goal is to make it through this stage of our evolutionary process - it's too late to clean up the world, it's already contaminated and chock full of prions. Hopefully, we can get it together and stop creating new prions before our systems are totally overwhelmed - stopping will give us a fighting chance to deal with what's already out there.

Originally posted by soficrow
.....continued from above.......

Sorry -screwed up the last 3 paragraphs. Here's the fix.



….Again - the normal prion protein already is a glycoprotein - when it misfolds, the chemistry does not change, only the shape or "conformation."

Moreover, research identifies the receptor for AGE's - not the AGE's themselves - as involved with the already misfolded amyloid-like protein in the disease process.

…..several cellular receptors for the amyloid-like protein fold have been identified: scavenger receptor A, CD36, receptor for advanced glycation end products, low density lipoprotein receptor-like protein, and scavenger receptor B type I (17). Moreover, these receptors are expressed on dendritic cells and could initiate an immune response against these proteins (34, 38).

The question remains - what causes the proteins to misfold in the first place?

The answer is - a HUGE range of environmental changes and exposures can cause proteins to misfold and become infectious. Some misfolding happens internally, due to exposures "chosen freely" by the individual, and AGE's might prove to be a cause of certain proteins' misfolding.

But the vast majority of infectious misfolded proteins in our world are created externally, and result from industrial processes and activities like drug manufacturing and food processing.

reply to post by soficrow


www.ncbi.nlm.nih.gov...

Prion diseases are fatal neurodegenerative diseases that occur either spontaneously or genetically or are caused by infection. Spontaneously occurring prion diseases are age related. The infectious agents, called prions, are proteinaceous infectious particles, composed mainly of the host-encoded prion protein (PrP) in a misfolded, insoluble, and aggregated isoform. Advanced glycation end products (AGEs) are well known to contribute to protein misfolding, insolubility, and aggregation. Thus, we studied if AGE-modification could influence PrP aggregation. We analyzed PrP preparations immunochemically to determine if they contain AGE-modified PrP. We also studied the influence of AGE modifications on the PrP aggregation process in vitro.

As I said before, I've read it in many journal articles that AGEs contribute to the misfolding of proteins. I'm off to do my own digging before I continue on this debate. I'll be back.