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The Case for Transmissible Alzheimer's Grows

blogs.scientificamerican.com

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Re: The Case for Transmissible Alzheimer's Grows

#101

Post by pbhjpbhj »

autokad wrote: post #52

> "In the original Alzheimer’s transmissibility study, scientists examined the brains of eight patients treated with prion-contaminated human growth hormone as children who decades later died from prion disease (out of over 30,000 people so treated, more than 200 died this way). " does anyone have any clarification on this? to me that is very alarming. that's about .67% which sounds small, but its int he ball bark of…

How does that compare to control? 200 : 30k sounds like it's lower than normal "infection" rate?

Re: The Case for Transmissible Alzheimer's Grows

#102

Post by toomuchtodo »

nonbel wrote: post #47

An increase in amyloids will be observed any time cells are malfunctioning for whatever reason. They are the most thermodynamically stable structure that polypeptides can form, and require constant housekeeping to prevent. Accumulation of amyloids is like failing to taking out the trash in your house. Afaik, there has never been a disease state checked for amyloids that failed to be associated with them (heart diseas…

Could amyloids be a proxy for aging in general? And systems declining in their ability to remove amyloids the cause of aging?

Re: The Case for Transmissible Alzheimer's Grows

#103

Post by pbhjpbhj »

DaiPlusPlus wrote: post #73
awakeasleep wrote: post #70

Earlier quoted context omitted.

Anything that you think of as 'corrosive' will generally break down proteins. Strong bases or acids.

Unfortunately they also tend to break down living tissue too. Relevant XKCD: https://xkcd.com/1217/

Does a [bullet from a] handgun [effectively] kill cancer cells in a petri dish? I'd expect it to smash the dish and move the cells but except for areas with localised heating not to really do anything else?

Re: The Case for Transmissible Alzheimer's Grows

#104

Post by nonbel »

toomuchtodo wrote: post #102
nonbel wrote: post #47

An increase in amyloids will be observed any time cells are malfunctioning for whatever reason. They are the most thermodynamically stable structure that polypeptides can form, and require constant housekeeping to prevent. Accumulation of amyloids is like failing to taking out the trash in your house. Afaik, there has never been a disease state checked for amyloids that failed to be associated with them (heart diseas…

Could amyloids be a proxy for aging in general? And systems declining in their ability to remove amyloids the cause of aging?

Or a symptom of aging. As for a proxy I doubt it would be much better than actual age.

Re: The Case for Transmissible Alzheimer's Grows

#105

Post by subroutine »

nonbel wrote: post #95
subroutine wrote: post #89

Earlier quoted context omitted.

There is a huge misconception about what is meant by the word "prion". Get this... there is only one (1) prion protein! All mammalian prion diseases are directly related to the PRNP gene. People talk about Mad Cow, Kuru, Creutzfeldt-Jacobs, Chronic Wasting Disease, Scrapie, and a dozen other diseases like they are not all manifestations of the same underlying problem with PRNP gene variants. People talk about "prions…

You don't share any links, but how would you reconcile this with the claims that amyloids are widespread. I posted about it here: https://news.ycombinator.com/item?id=19129157 Is it really the case that PRNP ( https://en.wikipedia.org/wiki/PRNP ) is the only known amyloid to be infectious?

My comment wasn't so much on the biology, or whether other proteins could display 'prion-like' behavior; it was more so to clarify what I think is a misuse/misunderstanding of the word 'prion'. I say this as someone who perpetuated this misuse until a few months ago, after reading an article about 'prions' in the retina, and spent half the day trying to figure out what the prion protein was, only to discover there was a gene that encoded PRioN Protein (PRNP); that is, we have a specific protein called 'prion protein' PrP. So to ask whether something is a prion suggests a misconception, since that's like asking "is insulin a keratin?" or "is melanopsin an actin?", and the answer would be, of course not, since those are all names of different proteins. Now, asking whether some protein X has properties similar to PrP is a totally legit question (i.e. "is X prion-like?" = great question; "is X a prion" = probably a misconception).

Re: The Case for Transmissible Alzheimer's Grows

#106

Post by escape_goat »

nonbel wrote: post #95
subroutine wrote: post #89

Earlier quoted context omitted.

There is a huge misconception about what is meant by the word "prion". Get this... there is only one (1) prion protein! All mammalian prion diseases are directly related to the PRNP gene. People talk about Mad Cow, Kuru, Creutzfeldt-Jacobs, Chronic Wasting Disease, Scrapie, and a dozen other diseases like they are not all manifestations of the same underlying problem with PRNP gene variants. People talk about "prions…

You don't share any links, but how would you reconcile this with the claims that amyloids are widespread. I posted about it here: https://news.ycombinator.com/item?id=19129157 Is it really the case that PRNP ( https://en.wikipedia.org/wiki/PRNP ) is the only known amyloid to be infectious?

You seem to be mixing terms a bit, so at risk of repeating things you know, I will explain what I am reading from what you've linked.

PRNP is the gene encoding for "the major prion protein." Several different errors in PRNP create versions of "the major prion protein" that can be folded in a way that is bad (the prion folding). However, that is not the only way in which the proteins can fold themselves.

When lots of these proteins stuck together in an 'amyloid' (starch-like) aggregation, a misfolded (bad) shape of the protein serves as a template, folding more and more instances of the protein into the bad shape.

We consider the shape to be 'bad' because it is associated with visible symptoms of disease.

It is the prion ('bad') folding of a protein which would be infectious.

There are lots of different proteins that create amyloids, but so far all symptoms of prion-type disease for which a cause has been found have turned out to be associated with errors in PRNP.

Re: The Case for Transmissible Alzheimer's Grows

#107

Post by nonbel »

escape_goat wrote: post #106
nonbel wrote: post #95

Earlier quoted context omitted.

You don't share any links, but how would you reconcile this with the claims that amyloids are widespread. I posted about it here: https://news.ycombinator.com/item?id=19129157 Is it really the case that PRNP ( https://en.wikipedia.org/wiki/PRNP ) is the only known amyloid to be infectious?

You seem to be mixing terms a bit, so at risk of repeating things you know, I will explain what I am reading from what you've linked. PRNP is the gene encoding for "the major prion protein." Several different errors in PRNP create versions of "the major prion protein" that can be folded in a way that is bad (the prion folding). However, that is not the only way in which the proteins can fold themselves. When lots of…

>"so far all symptoms of prion-type disease for which a cause has been found have turned out to be associated with errors in PRNP."

Thanks, this is an interesting new fact to me if true. Is there a source for it?

I don't mean a source proving there are no others or something else silly like that. I mean like a review article that mentions they couldn't find any publication about any amyloid beyond PRNP-derived ones being transmitted.

Re: The Case for Transmissible Alzheimer's Grows

#108

Post by nonbel »

subroutine wrote: post #105
nonbel wrote: post #95

Earlier quoted context omitted.

You don't share any links, but how would you reconcile this with the claims that amyloids are widespread. I posted about it here: https://news.ycombinator.com/item?id=19129157 Is it really the case that PRNP ( https://en.wikipedia.org/wiki/PRNP ) is the only known amyloid to be infectious?

My comment wasn't so much on the biology, or whether other proteins could display 'prion- like ' behavior; it was more so to clarify what I think is a misuse/misunderstanding of the word 'prion'. I say this as someone who perpetuated this misuse until a few months ago, after reading an article about 'prions' in the retina, and spent half the day trying to figure out what the prion protein was, only to discover there…

Thanks. It is also not clear to me after a quick search whether any amyloid has been called "infectious" other than ones derived from the PRNP sequence. It is very interesting.

Re: The Case for Transmissible Alzheimer's Grows

#109

Post by subroutine »

nonbel wrote: post #108
subroutine wrote: post #105

Earlier quoted context omitted.

My comment wasn't so much on the biology, or whether other proteins could display 'prion- like ' behavior; it was more so to clarify what I think is a misuse/misunderstanding of the word 'prion'. I say this as someone who perpetuated this misuse until a few months ago, after reading an article about 'prions' in the retina, and spent half the day trying to figure out what the prion protein was, only to discover there…

Thanks. It is also not clear to me after a quick search whether any amyloid has been called "infectious" other than ones derived from the PRNP sequence. It is very interesting.

I'm telling you-- i went down the prion rabbit hole myself recently and the entire path is littered with misconception and inconsistencies in how the term "prion" is being used.

One place to start other than wikipedia is this cdc site that lists know prion diseases...

https://www.cdc.gov/prions/index.html

After some digging, I concluded that all the diseases they listed are related to PRNP. Please, please, correct me if I'm wrong.

I'm actually going to chat with a friend in a few minutes who is a postdoc at MIT studying protein (mis)folding, and said he could help clarify. (i'll relay any new insights...)

Re: The Case for Transmissible Alzheimer's Grows

#110

Post by sugarpile »

SideburnsOfDoom wrote: post #18

Does this line of inquiry mesh at all with the idea that "Gum disease–causing bacteria could spur Alzheimer’s" Or are they competing hypotheses? reported here in January: https://news.ycombinator.com/item?id=18987015

My concern is that having general high amounts of inflammation in your body alone increases your risk for Alzheimer's. As someone with inflammation diseases galore (including gum disease), I hope I'm just making inferences where there's no data to support them. Anyone know if that's the case?
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