4 ms·

My first thought is a relationship with glutamate excitotoxicity. Fronto-temporal dementia is known to be related to glutamate. If that’s lumped in as part of t

by jf- 8y ago

My first thought is a relationship with glutamate excitotoxicity. Fronto-temporal dementia is known to be related to glutamate. If that’s lumped in as part of the dementia cohort that may help explain the result.

Herodotus38 8y ago
Probably not a large factor because the prevalence of frontiers-temporal dementia is very small compared to vascular, Alzheimer's, Parkinson's. Anecdotally I see it in less than 1% of dementia patients. Incidence of FTD is around 2.7-4.1 per 100,000 people. Incidence for Alzheimer's is estimated to be roughly 10.5 per 1000 So although it's a good thought to have about the correlation, even if 100% of FTD cases were caused by that mechanism I don't think you'd see the difference they saw in the study. Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932112/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932112/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405821/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405821/
- jf- 8y ago
  If I remember correctly, the mechanism underlying the glutamate toxicity is mutant SOD, which is made as a response to oxidative stress. The glutamate is simply an excitory stimulus that makes free radicals which need to be mopped up by something. Could be that other proteinopathies are a similar reaction to oxidative stress, and something that promotes GABA, such as alcohol, has a beneficial effect. But of course I’m only speculating.
  - Herodotus38 8y ago
    I'm not knowledgeable enough about the biology to really add much to what you said there either, even though I deal with the end results. Systems biology is one of those areas where I think AI will make a huge difference in the future. If you are interested in some thoughts on this listen to the first hour and a half talk by Craig Mundie (you can skip first 20 minutes of intro by Collins) of this recent NIH videocast on AI in medicine: https://videocast.nih.gov/summary.asp?live=28053&bhcp=1 https://videocast.nih.gov/summary.asp?live=28053&bhcp=1

by jf- 8y ago

Herodotus38 8y ago

Probably not a large factor because the prevalence of frontiers-temporal dementia is very small compared to vascular, Alzheimer's, Parkinson's. Anecdotally I see it in less than 1% of dementia patients. Incidence of FTD is around 2.7-4.1 per 100,000 people. Incidence for Alzheimer's is estimated to be roughly 10.5 per 1000 So although it's a good thought to have about the correlation, even if 100% of FTD cases were caused by that mechanism I don't think you'd see the difference they saw in the study. Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932112/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932112/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405821/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405821/

jf- 8y ago
If I remember correctly, the mechanism underlying the glutamate toxicity is mutant SOD, which is made as a response to oxidative stress. The glutamate is simply an excitory stimulus that makes free radicals which need to be mopped up by something. Could be that other proteinopathies are a similar reaction to oxidative stress, and something that promotes GABA, such as alcohol, has a beneficial effect. But of course I’m only speculating.
- Herodotus38 8y ago
  I'm not knowledgeable enough about the biology to really add much to what you said there either, even though I deal with the end results. Systems biology is one of those areas where I think AI will make a huge difference in the future. If you are interested in some thoughts on this listen to the first hour and a half talk by Craig Mundie (you can skip first 20 minutes of intro by Collins) of this recent NIH videocast on AI in medicine: https://videocast.nih.gov/summary.asp?live=28053&bhcp=1 https://videocast.nih.gov/summary.asp?live=28053&bhcp=1