study identifies sildenafil(viagra) as potential alzheimers treatment

[allone]

from this source; https://medicalxpress.com/news/2021-12-sildenafil-candidate-drug-alzheimer-disease.html

discussion

 

[Skorpio]

I am skeptical of anything alzheimer's disease related because of how little we understand about its eitology. (is amyloid beta a symptom or a driver? What about tau? How do you treat a disease when it is only apparent after significant damage has occured?)

However i do like correlational studies with common drugs (big populations allow for good power), and Viagra is benign enough to pretreat and not cause a huge health burden.

I would be very interested to see the putative mechanism tested rigorously.

But these days I'll take what i can get with alzheimers, I'm bummed the gingipain hypothesis didn't pan out (really convincing pre clinical data found a lot of gingivitis in alzheimers patients, and you could give mice pathology by infecting them with this specific bacteria. They made a drug that blocked this effect without killing the bacteria (low chance of resistence as no selection pressure), but then it failed clinical trials because it didn't produce an effect.

 

[4meSM]

I wonder if this could have something to do with blood flow/ oxygenation or if it's working via a more selective mechanism. I recall reading something about sildenafil having a positive effect on cerebral blood flood, but only in compromised subjects (diabetics, etc...). I know it's able to cross the BBB but I'm not sure whether phosphodiesterase-5 is significantly expressed in the human brain or not. Seems interesting given that obstructive sleep apnea is somewhat correlated with alzheimer's disease.

I don't know much about sildenafil but it's supposed to be a fairly selective inhibitor isn't it?

 

[CFC]

I wonder if this could have something to do with blood flow/ oxygenation or if it's working via a more selective mechanism. I recall reading something about sildenafil having a positive effect on cerebral blood flood, but only in compromised subjects (diabetics, etc...). I know it's able to cross the BBB but I'm not sure whether phosphodiesterase-5 is significantly expressed in the human brain or not. Seems interesting given that obstructive sleep apnea is somewhat correlated with alzheimer's disease.

I don't know much about sildenafil but it's supposed to be a fairly selective inhibitor isn't it?

Tests in petri dishes suggest sildenafil has a direct effect promoting neuronal growth as well as an inhibitory effect on both tau tangles and B-amyloid. So that would likely be in addition to any indirect effects via improved cerebral blood flow (which you also see with things like citrulline).

 

[CFC]

is amyloid beta a symptom or a driver?

More than likely it's both.

I'm bummed the gingipain hypothesis didn't pan out

Most reductionist hypotheses that posit a single or narrow number of causes will probably 'fail'. However, it's still likely they're all involved in disease progress to varying degrees depending on each person's circumstances and genetic predispositions.