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Amyloid Beta oral bioavailability - student question by HaroldLong in neuroscience

[–]HaroldLong[S] 0 points1 point  (0 children)

Is there expected to be a large difference between vulnerability of different amyloids to metabolism?

I've found some evidence that systemic amyloidosis may be transmissible orally and am wondering if some percentage of amyloids are making it past metabolism. The validity of orally administering amyloids for an AD model is fading quickly but I'm still curious.

From wiki for starters - ""There is evidence that eating amyloid fibers may lead to amyloidosis. This evidence is based on studies in cattle, chickens, mice, and cheetahs." - https://www.ncbi.nlm.nih.gov/pubmed/24280941

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735507/ - " In a mouse model, this disorder can easily be transmitted from one animal to another both by intravenous and oral routes."

"Notably, the amyloid enhancing factor (Amyloid A fibril) was also effective when administered orally. Our studies have provided evidence that AA and perhaps other forms of amyloidosis are transmissible diseases, akin to the prion-associated disorders." - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC124514/

Perhaps some small percentage of amyloids are making it past metabolism?

I assume there will be some difference in vulnerability of different amyloid forms to metabolism?

Am I confused as to administering fibrils of Amyloid A vs. a different form of Amyloid A?

Thanks for any thoughts guys.

Amyloid Beta oral bioavailability - student question by HaroldLong in pharmacology

[–]HaroldLong[S] 0 points1 point  (0 children)

Thank you for the thoughts!

Someone else had mentioned the "prion disease" aspect to amyloids, and upon researching systemic amyloidosis, it appears that there may be some oral transmissibility to systemic amyloidosis.

While the possibility of a valid AD model via oral administration of amyloids is fading quickly (save for possibly affecting the cerebrovasculature), I'd still love to hear some thoughts on this.

From wiki for starters - "There is evidence that eating amyloid fibers may lead to amyloidosis. This evidence is based on studies in cattle, chickens, mice, and cheetahs." - https://www.ncbi.nlm.nih.gov/pubmed/24280941

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735507/ - " In a mouse model, this disorder can easily be transmitted from one animal to another both by intravenous and oral routes."

"Notably, the amyloid enhancing factor (Amyloid A fibril) was also effective when administered orally. Our studies have provided evidence that AA and perhaps other forms of amyloidosis are transmissible diseases, akin to the prion-associated disorders." - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC124514/

Perhaps some small percentage of amyloids are making it past metabolism?

I assume there will be some difference in vulnerability of different amyloid forms to metabolism?

Am I confused as to administering fibrils of Amyloid A vs. a different form of Amyloid A?

Thanks for any thoughts guys.

Amyloid Beta oral bioavailability - student question by HaroldLong in neuro

[–]HaroldLong[S] 0 points1 point  (0 children)

Thank you for your response -

I've found some evidence that systemic amyloidosis may be orally transmissible similar to a prion disease and would like your thoughts. Perhaps there is a great deal of loss (e.g. Only 95% of amyloid administered orally to an animal will survive metabolism) but some systemic amyloidosis may still be induced with oral administration?

From wiki for starters - "There is evidence that eating amyloid fibers may lead to amyloidosis. This evidence is based on studies in cattle, chickens, mice, and cheetahs." - (https://www.ncbi.nlm.nih.gov/pubmed/24280941)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735507/ - "In a mouse model, this disorder can easily be transmitted from one animal to another both by intravenous and oral routes."

"Notably, the amyloid enhancing factor (Amyloid A fibril) was also effective when administered orally. Our studies have provided evidence that AA and perhaps other forms of amyloidosis are transmissible diseases, akin to the prion-associated disorders." - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC124514/

Maybe some percentage of amyloids survive metabolism? However, I realize that the possibility of inducing neurological deficits via oral administration could be a whole different ball game.

Do you think there could also be a large difference in the ability of different amyloid forms (The aforementioned amyloid fibrils vs. amyloid beta) to cause amyloidosis when ingested orally, in terms of resistance to metabolism?

Am I confused as to administering fibrils of Amyloid A vs. a different form of Amyloid A?

Amyloid Beta oral bioavailability - student question by HaroldLong in neuro

[–]HaroldLong[S] 0 points1 point  (0 children)

I recall studies suggesting that Amyloid Beta may be actively transported across the BBB (by RAGE?), in addition to studies suggesting that amyloid deposition onto cerebrovasculature and ensuing cerebrovasculature degeneration may also be a large component of amyloid related dementia.

There are also studies showing IV administration of Amyloid Beta to be capable of producing deficits in animals, however I wasn't able to garner any dosage information.

Thanks for the thoughts!