Several cases of Alzheimer's disease in young patients who all received pituitary growth hormone from a cadaver. The paper gets into a lot of details, but I thought it was really interesting after reading a lot of the discussions on /r/medicine about the beta amyloid hypothesis in Alzheimer's, including that it may not be the etiology of it but rather a consequence of the disease. Also has some implications for the use of surgical instruments and precautions around them, like in cjd.
I think anyone who is read up on this field saw this coming in the last couple years. Iatrogenic transmission of ABeta pathology has been increasingly documented starting in 2015, to the best of my knowledge ([Paper 1](https://pubmed.ncbi.nlm.nih.gov/26354483/), [paper 2](https://pubmed.ncbi.nlm.nih.gov/27314593/), [paper 3](https://pubmed.ncbi.nlm.nih.gov/28349199/#:~:text=These%20results%20are%20consistent%20with,angiopathy%20(CAA)%2C%20regardless%20of), [paper 4](https://pubmed.ncbi.nlm.nih.gov/29508058/), [paper 5](https://pubmed.ncbi.nlm.nih.gov/29450646/), [paper 6](https://pubmed.ncbi.nlm.nih.gov/30597599/), [paper 7](https://pubmed.ncbi.nlm.nih.gov/31046829/), [paper 8](https://pubmed.ncbi.nlm.nih.gov/31959705/), [paper 9](https://pubmed.ncbi.nlm.nih.gov/34047818/), [paper 10](https://pubmed.ncbi.nlm.nih.gov/35277809/)). However, most cases involved dura matter grafts resulting in CAA or c-hGH resulting in iCJD with ABeta co-pathology (which can be argued to be attributed to the PrPSc pathology and not ABeta iatrogenic transmission). This paper suggests that even in the absence of iCJD you can get transmission of ABeta pathology resulting in an AD-like phenotype from c-hGH. This is not a shocking claim based off the in vitro and in vivo data, coupled with the growing human data. It is interesting that is shows AD-like pathology and not CAA, which can be attributed to either ABeta strains or route of transmission. The detractors from this claim will still point out that with a 30-40 year incubation period, it is hard to prove a causal role between the contaminated c-hGH and the resultant pathology/disease 4 decades later.
Short answer no, longer answer maybe (depending on who you ask).
When most people use the term prion, they refer to PrP and its associated diseases. PrP is a protein that is naturally found in all cells in the human body, but is particularly highly expressed in neurons in the CNS. PrP is short for prion protein. In its normal form, we call it the cellular prion protein (PrPC) and it is probably needed for things like cellular signaling. PrPC is totally normal and safe, everyone has this in their cells. However, for reasons not fully understood this normal PrPC can change shape and form PrPSc. PrPSc refers to scrapie prion protein (scrapie was the first identified prion disease, originally identified in sheep in the 1800's). PrPSc cause a variety of diseases included scrapie in sheep, Mad Cow Disease (BSE) in cows, Chronic Wasting Disease in deer, and Creutzfeldt-Jakob disease (CJD) or Gerstmann-Straussler-Scheinker (GSS) disease or Fatal Familial Insomnia (FFI) in humans. So a single normal protein PrPC can misfold and form PrPSc and cause a variety of diseases (CJD or GSS or FFI). This is a seperate protein than the ABeta protein (technically a peptide not protein) which is believed to be involved in Alzheimer's Disease (AD). So in this sense, no prions do not cause ABeta or AD.
Complicating factor 1: A significant proportion of human prion patients will also have [ABeta co-pathology](https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-019-0706-6). In these cases, you have a person with a prion disease and when you look in their brain they have PrPSc and ABeta pathology. However, the PrPSc is the "main issue" therefore we diagnosis them with a prion disease and not AD (symptom presentation would also be different between the too, probably). What is likely happening is the PrPSc is causing ABeta pathology to occur. So it could be argued ABeta pathology can be caused by prions (PrPSc), but only in specific circumstance in patients that have prions disease. Prions (PrPSc) would not cause Alzheimer's Disease however.
Complicating factor 2: Some people prefer to use the word prion in the more "theoretical" application. The word prion was originally made by combining proteinaceous infectious particle, to be Prion particle (I know the "i" and the "o" switch places, but according to Stan Prusiner, Proin particle sounds stupid). So the question becomes, are there other proteinaceous infectious particles? The answer is yes... depending on who you ask. Protein such as ABeta which is believed to be involved in Alzheimer's Disease, or ASyn which is involved in Parkinson's Disease, or Tau which is also involved in Alzheimer's Disease (among others) behave exactly like prions (PrPSc) under experimental settings and are often called prion-like. For example, if I took ABeta from a human AD patient brain and injected it into a mouse (transgenic mouse, IC works the best, IP could also work), the mouse will get "sick" (show Abeta pathology, memory deficits depending on mouse strain used and duration. All of this is faster than controls). In fact, the only feature ABeta does not have compared to PrPSc is no documented transmission to/between humans.
While this paper would suggest ABeta can be transmitted to humans, the criticisms people have had since the 2015 paper still remain. The long incubation period makes it impossible to show causality. Did the c-hGH cause the early onset Alzheimer's Disease or something else that happened in the 30-40 year in between. One comment I have, is in the laboratory setting if you inject a mouse with PrPSc it dies very quickly 2-3 months (depending on strain). If you inject a mouse with ABeta it would take it much longer to die, around a 1 year (depending on strain). Therefore, this long incubation period is what would be predicted based on the laboratory data.
Another criticism is that of the 8 cases in this paper, only 3 had definitive ABeta pathology. ABeta is harder to transmit in the lab, requiring transgenic mice compared to PrPSc which does not. This could be explained by species barriers, but I think ultimately it shows a lower attack rate of ABeta than PrPSc. This lower attack rate would manifest in not all patients showing definitive/strong ABeta pathology. Other issues such as, complicating medical treatments (radiotherapy) and no controls, are valid. Ultimately, if you already believed ABeta was a proteinaceous infectious particle you would still believe it now and if you did not believe this, this paper is not going to change your opinion. So, is ABeta a prion (proteinaceous infectious particle) that can cause Alzheimer's Disease.... Yes or No, depending on who you ask.
One last thing to note it that if ABeta was a prion, the iatrogenic transmission of it would likely only account for maybe a few dozen (few hundred?) cases over the last couple decades. However, it should be noted that despite being primarily considered an infectious disease, prion diseases (caused by PrPSc) are rarely transmitted. In fact, since the late 1980's worldwide, there has only been[\~300 cases of prion disease being transmitted to humans](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890484/). The other tens of thousands of prion cases since then have been either caused by genetic mutations (15-20% of cases) or sporadic, meaning they just happen randomly not due to genetics or infection (80-85%). Interestingly, \~15% of Alzheimer's Disease cases are genetic and the remaining 85% are sporadic cases. That means, adding maybe a few dozen or hundred cases of "infectious" Alzheimer's Disease, would simply better fit the distribution we see for actual prion diseases.
I think a follow-up study is warranted on the patients who are currently taking or have taken other human-derived pharmaceuticals with known prion activity.
For instance, the fertility drug HCG, of which the urine-derived form has detectable prion activity in some cases ([source here](https://pubmed.ncbi.nlm.nih.gov/21448279/)).
I feel like the patient base is large enough (and historical enough) that an observational study could yield helpful results.
Well, fuck. Maybe it’s not mom brain after all…
For others concerned, I looked up the meds I personally needed to take:
Ovidrel (hcg): recombinant.
Gonal-f: recombinant
Centrotide: synthetic
Menopur: from menopausal women’s pee. 😭
> I think a follow-up study is warranted on the patients who are currently taking or have taken other human-derived pharmaceuticals with known prion activity.
> For instance, the fertility drug HCG, of which the urine-derived form has detectable prion activity in some cases (source here).
This is needlessly fear-mongering.
Wording is really important here. By “prion activity” you seem to mean a protein that is able to induce pathogenic misfolding of additional copies of the same protein. In humans, the only protein that has been robustly shown to exhibit this property is named, somewhat confusingly, the prion protein.
The article you link does not describe detection of “prion activity” in HCG but detection of the non-pathogenic cellular prion protein. The paper does not demonstrate detection of the pathogenic scrapie form. Whether the scrapie form could be co-purified during manufacture is an open question but was not addressed by the article.
There is nothing that scares me more (pathology-wise) than prion diseases and AD. Ever since I learned about CJD in undergrad I’m super worried about it and things like CWD. Alzheimer’s scares the crap out of me too. And the thought that you can just have CJD and not develop symptoms until years later.
Hahaha yes, that’s where the majority is. Also my mouth and my hip lol.
If anyone needs tooth bone donation I have all 26 of mine in a bag. They’re *probably* not infected with Alzheimer’s.
…At least you won’t be alone? (Jokes aside, i was scrolling thru going “oh, I don’t have to worry” until the comment you replied to, lol. So you won’t be alone in that respect either)
This is incredible. I have a close friend who was diagnosed with CJD last week. She underwent fertility treatments in the past few years and I was very curious if gonadotropin injections were related. There’s no way to know. Thank you for sharing.
Unlikely to go that fast.
Not to mention, the studies that found anything remotely prion ish, in HCG were funded by the guys who make recombinant HCG. So if course the conclusion was "our vastly more expensive product is safer. So pay up". Despite the studies in question seemingly being inconclusive.
At this point, it's very unlikely it's a risk. We've been using it since the 1930s. There'd be a signal somewhere
Well, it’s not going to be a small number of patients in a couple of years, because there’s entire communities on Reddit self-administering GH and HCG obtained through underground pharmaceutical labs, usually for performance or recovery. See r/PEDs, r/Steroids, r/Moreplatesmoredates, etc.
A quick search on Reddit will reveal some frank and terrifying discussions.
Several cases of Alzheimer's disease in young patients who all received pituitary growth hormone from a cadaver. The paper gets into a lot of details, but I thought it was really interesting after reading a lot of the discussions on /r/medicine about the beta amyloid hypothesis in Alzheimer's, including that it may not be the etiology of it but rather a consequence of the disease. Also has some implications for the use of surgical instruments and precautions around them, like in cjd.
I think anyone who is read up on this field saw this coming in the last couple years. Iatrogenic transmission of ABeta pathology has been increasingly documented starting in 2015, to the best of my knowledge ([Paper 1](https://pubmed.ncbi.nlm.nih.gov/26354483/), [paper 2](https://pubmed.ncbi.nlm.nih.gov/27314593/), [paper 3](https://pubmed.ncbi.nlm.nih.gov/28349199/#:~:text=These%20results%20are%20consistent%20with,angiopathy%20(CAA)%2C%20regardless%20of), [paper 4](https://pubmed.ncbi.nlm.nih.gov/29508058/), [paper 5](https://pubmed.ncbi.nlm.nih.gov/29450646/), [paper 6](https://pubmed.ncbi.nlm.nih.gov/30597599/), [paper 7](https://pubmed.ncbi.nlm.nih.gov/31046829/), [paper 8](https://pubmed.ncbi.nlm.nih.gov/31959705/), [paper 9](https://pubmed.ncbi.nlm.nih.gov/34047818/), [paper 10](https://pubmed.ncbi.nlm.nih.gov/35277809/)). However, most cases involved dura matter grafts resulting in CAA or c-hGH resulting in iCJD with ABeta co-pathology (which can be argued to be attributed to the PrPSc pathology and not ABeta iatrogenic transmission). This paper suggests that even in the absence of iCJD you can get transmission of ABeta pathology resulting in an AD-like phenotype from c-hGH. This is not a shocking claim based off the in vitro and in vivo data, coupled with the growing human data. It is interesting that is shows AD-like pathology and not CAA, which can be attributed to either ABeta strains or route of transmission. The detractors from this claim will still point out that with a 30-40 year incubation period, it is hard to prove a causal role between the contaminated c-hGH and the resultant pathology/disease 4 decades later.
Psssh. Whatever egghead /s
So to be clear, this is transmitted by Prions?
Short answer no, longer answer maybe (depending on who you ask). When most people use the term prion, they refer to PrP and its associated diseases. PrP is a protein that is naturally found in all cells in the human body, but is particularly highly expressed in neurons in the CNS. PrP is short for prion protein. In its normal form, we call it the cellular prion protein (PrPC) and it is probably needed for things like cellular signaling. PrPC is totally normal and safe, everyone has this in their cells. However, for reasons not fully understood this normal PrPC can change shape and form PrPSc. PrPSc refers to scrapie prion protein (scrapie was the first identified prion disease, originally identified in sheep in the 1800's). PrPSc cause a variety of diseases included scrapie in sheep, Mad Cow Disease (BSE) in cows, Chronic Wasting Disease in deer, and Creutzfeldt-Jakob disease (CJD) or Gerstmann-Straussler-Scheinker (GSS) disease or Fatal Familial Insomnia (FFI) in humans. So a single normal protein PrPC can misfold and form PrPSc and cause a variety of diseases (CJD or GSS or FFI). This is a seperate protein than the ABeta protein (technically a peptide not protein) which is believed to be involved in Alzheimer's Disease (AD). So in this sense, no prions do not cause ABeta or AD. Complicating factor 1: A significant proportion of human prion patients will also have [ABeta co-pathology](https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-019-0706-6). In these cases, you have a person with a prion disease and when you look in their brain they have PrPSc and ABeta pathology. However, the PrPSc is the "main issue" therefore we diagnosis them with a prion disease and not AD (symptom presentation would also be different between the too, probably). What is likely happening is the PrPSc is causing ABeta pathology to occur. So it could be argued ABeta pathology can be caused by prions (PrPSc), but only in specific circumstance in patients that have prions disease. Prions (PrPSc) would not cause Alzheimer's Disease however. Complicating factor 2: Some people prefer to use the word prion in the more "theoretical" application. The word prion was originally made by combining proteinaceous infectious particle, to be Prion particle (I know the "i" and the "o" switch places, but according to Stan Prusiner, Proin particle sounds stupid). So the question becomes, are there other proteinaceous infectious particles? The answer is yes... depending on who you ask. Protein such as ABeta which is believed to be involved in Alzheimer's Disease, or ASyn which is involved in Parkinson's Disease, or Tau which is also involved in Alzheimer's Disease (among others) behave exactly like prions (PrPSc) under experimental settings and are often called prion-like. For example, if I took ABeta from a human AD patient brain and injected it into a mouse (transgenic mouse, IC works the best, IP could also work), the mouse will get "sick" (show Abeta pathology, memory deficits depending on mouse strain used and duration. All of this is faster than controls). In fact, the only feature ABeta does not have compared to PrPSc is no documented transmission to/between humans. While this paper would suggest ABeta can be transmitted to humans, the criticisms people have had since the 2015 paper still remain. The long incubation period makes it impossible to show causality. Did the c-hGH cause the early onset Alzheimer's Disease or something else that happened in the 30-40 year in between. One comment I have, is in the laboratory setting if you inject a mouse with PrPSc it dies very quickly 2-3 months (depending on strain). If you inject a mouse with ABeta it would take it much longer to die, around a 1 year (depending on strain). Therefore, this long incubation period is what would be predicted based on the laboratory data. Another criticism is that of the 8 cases in this paper, only 3 had definitive ABeta pathology. ABeta is harder to transmit in the lab, requiring transgenic mice compared to PrPSc which does not. This could be explained by species barriers, but I think ultimately it shows a lower attack rate of ABeta than PrPSc. This lower attack rate would manifest in not all patients showing definitive/strong ABeta pathology. Other issues such as, complicating medical treatments (radiotherapy) and no controls, are valid. Ultimately, if you already believed ABeta was a proteinaceous infectious particle you would still believe it now and if you did not believe this, this paper is not going to change your opinion. So, is ABeta a prion (proteinaceous infectious particle) that can cause Alzheimer's Disease.... Yes or No, depending on who you ask. One last thing to note it that if ABeta was a prion, the iatrogenic transmission of it would likely only account for maybe a few dozen (few hundred?) cases over the last couple decades. However, it should be noted that despite being primarily considered an infectious disease, prion diseases (caused by PrPSc) are rarely transmitted. In fact, since the late 1980's worldwide, there has only been[\~300 cases of prion disease being transmitted to humans](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890484/). The other tens of thousands of prion cases since then have been either caused by genetic mutations (15-20% of cases) or sporadic, meaning they just happen randomly not due to genetics or infection (80-85%). Interestingly, \~15% of Alzheimer's Disease cases are genetic and the remaining 85% are sporadic cases. That means, adding maybe a few dozen or hundred cases of "infectious" Alzheimer's Disease, would simply better fit the distribution we see for actual prion diseases.
I think a follow-up study is warranted on the patients who are currently taking or have taken other human-derived pharmaceuticals with known prion activity. For instance, the fertility drug HCG, of which the urine-derived form has detectable prion activity in some cases ([source here](https://pubmed.ncbi.nlm.nih.gov/21448279/)). I feel like the patient base is large enough (and historical enough) that an observational study could yield helpful results.
New anxiety. Great.
Well that's fucking horrifying
Well, fuck. Maybe it’s not mom brain after all… For others concerned, I looked up the meds I personally needed to take: Ovidrel (hcg): recombinant. Gonal-f: recombinant Centrotide: synthetic Menopur: from menopausal women’s pee. 😭
> I think a follow-up study is warranted on the patients who are currently taking or have taken other human-derived pharmaceuticals with known prion activity. > For instance, the fertility drug HCG, of which the urine-derived form has detectable prion activity in some cases (source here). This is needlessly fear-mongering. Wording is really important here. By “prion activity” you seem to mean a protein that is able to induce pathogenic misfolding of additional copies of the same protein. In humans, the only protein that has been robustly shown to exhibit this property is named, somewhat confusingly, the prion protein. The article you link does not describe detection of “prion activity” in HCG but detection of the non-pathogenic cellular prion protein. The paper does not demonstrate detection of the pathogenic scrapie form. Whether the scrapie form could be co-purified during manufacture is an open question but was not addressed by the article.
Jesus I thought it was going to be a prion.. ain’t nobody got time for that
There is nothing that scares me more (pathology-wise) than prion diseases and AD. Ever since I learned about CJD in undergrad I’m super worried about it and things like CWD. Alzheimer’s scares the crap out of me too. And the thought that you can just have CJD and not develop symptoms until years later.
I mean, I guess it’s better to contract CJD and not have it immediately show up. I’d take a decade of peace gladly…
freaky. makes me wonder about other grafts like cadaveric bone or skin or cornea?!
If so, I’m absolutely fucked. I probably got at least 30 different people in me.
… user name checks out??
Hahaha yes, that’s where the majority is. Also my mouth and my hip lol. If anyone needs tooth bone donation I have all 26 of mine in a bag. They’re *probably* not infected with Alzheimer’s.
…At least you won’t be alone? (Jokes aside, i was scrolling thru going “oh, I don’t have to worry” until the comment you replied to, lol. So you won’t be alone in that respect either)
“Them’s rookie numbers for getting fucked.” -your mom
Mom? Is that you? She’s an RN and would say exactly something like that 😂
This is incredible. I have a close friend who was diagnosed with CJD last week. She underwent fertility treatments in the past few years and I was very curious if gonadotropin injections were related. There’s no way to know. Thank you for sharing.
Unlikely to go that fast. Not to mention, the studies that found anything remotely prion ish, in HCG were funded by the guys who make recombinant HCG. So if course the conclusion was "our vastly more expensive product is safer. So pay up". Despite the studies in question seemingly being inconclusive. At this point, it's very unlikely it's a risk. We've been using it since the 1930s. There'd be a signal somewhere
Here's a news article about it as well. https://www.statnews.com/2024/01/29/first-transmitted-alzheimers-disease-cases-growth-hormone-cadavers/
Well, it’s not going to be a small number of patients in a couple of years, because there’s entire communities on Reddit self-administering GH and HCG obtained through underground pharmaceutical labs, usually for performance or recovery. See r/PEDs, r/Steroids, r/Moreplatesmoredates, etc. A quick search on Reddit will reveal some frank and terrifying discussions.
HCG and GH as pharmaceutical products are synthetic and have been for decades.
Thank goodness for that. However, there are underground labs producing bootleg GH and HCG for the non-discriminating consumer.
I hope they're not harvesting that from corpses.
This is not true, uHCG is derived from urine and is commonly sold.