RE: Human Longevity, SRT1, and Alzheimers Disease: A Brief Review of A Recent Publication
One of your links had this
. Previously, we have shown that miR-132 can regulate tau alternative splicing in vitro by targeting polypyrimidine tract-binding protein 2 (PTBP2), whereas miR-132 levels correlate with tau splicing defects in PSP cases (40).
Which led to this https://academic.oup.com/hmg/article/20/20/4016/697377
We demonstrate that miR-132 directly targets the neuronal splicing factor polypyrimidine tract-binding protein 2 (PTBP2), which protein levels were increased in PSP patients. miR-132 overexpression or PTBP2 knockdown similarly affected endogenous 4R:3R-tau ratios in neuronal cells. Finally, we provide evidence that miR-132 is inversely correlated with PTBP2 during post-natal brain development at the time when 4R-tau becomes expressed. Taken together, these results suggest that changes in the miR-132/PTBP2 pathway could contribute to the abnormal splicing of tau exon 10 in the brain, and sheds light into the potential role played by miRNAs in a subset of tauopathies.
and
Blocking endogenous miRNA levels with antisense probes reversed the effects of miR-124, miR-132, miR-137 and miR-153 on 4R:3R-tau ratios (Supplementary Material, Fig. S2), indicating that physiologically expressed miRNAs can regulate tau isoform abundance. Interestingly, miR-9 and miR-137 increased, while miR-132 decreased, total tau protein levels (Fig. 1A and B).
Yeah, I guess researchers don't know exactly why this all is, they just found the connections between the miRs and tau.
Well, there have been clear established links to, for example, dairy and red meat consumption and AD, and those things are also linked to inflammation and poor circulatory health, and about a quarter of AD is vascular and AD itself is contemplated by some to be an inflammation-related disease so...
Yep, lots of interesting findings, but not a clear picture of how it all pieces together. For that, we will need... more data.
Yes and? Correlation is not causation. I just don't believe the data yet. I need more information and stronger relationships! I find a lot of things interesting, I just don't ascribe to any of it being the answer. If that makes any sense...
Yeah, more data is always nice. I do think the next few decades will be interesting as we've already seen increased incidents in countries that previously didn't have many, and more countries seem to be adopting a western lifestyle.
I don't think any single factor will ever be discovered to be the cause, I just think that a slew of factors increase the chance the brain reaches the tipping point where things start to go wonky and the brain is creating more tangles, failing to successfully create new neurons, and isn't properly flushing out the tangles during sleep.
Like, for example, statins, they say they aren't sure if they help or not, but on the one hand you have people who are perhaps suffering more from the vascular aspects and it might help them a bit more than others, but on the other hand it might make things worse for some if there is some interaction where it's interfering with myelin health.
Well that's sort of the deal with medicine, everything has a trade off. Incorporate drugs to modify aspects of your bodies function when the net effect will extend your life. Their ain't no such thing as a free lunch. I take hypertension medication, knowing full well that it's damaging my circulation. I must work to mitigate that damage, but irregardless, I would die much sooner from my blood pressure damaging my arteries and organs the opposite way, then I will from the BP meds.
Same goes for everything, statins are no excepton. They don't come with out a cost, but for some, that cost is less then not using.
I wish people thought more about what medications are, and didn't just think they were cost free.