1230 replies to this topic

[mag1]

res, you said it eloquently.

 

The one thing that I am not sure about is the actual differential diagnosis of AD.

The FDA really does not require a finely grained distinction about dementia.

Often patients are just lumped into the box other (that is, AD).

There has even been quite a bit of confusion about what AD actually means:

In some of the recent clinical trials about 40% of patients did not even have AD.

 

It would be such a large step forward if we could create diagnostic subgroups such as copper AD etc. .

Yet, I suppose the pharmas love to treat a broad group of patients with medicines that probably are not that helpful to many of the patients.

For example, when I went through our loved ones 23andme file, SNPs kept popping up that said that Aricept would not be that helpful.

No one seemed very motivated to look into this.

 

We have probably reached a point in which approved drugs will need to be shown to be effective across specific genotypes and not just on average.

Edited by mag1, 20 January 2016 - 06:16 AM.

[resveratrol_guy]

Logic is right: virgin coconut oil is fantastic for the brain, if one can tolerate its digestion. Beware that cheaper brands can be somewhat rancid, as the majority of coconut oil is produced in the Philippines and transported in unhygienic trucks. Personally, I prefer Now Sports MCT, which has no stench, although it lacks the lauric acid that he mentioned. The only problem with coconut oil is that it's calorically dense. To those of us on caloric restriction, this isn't practical, so personally I don't take much anymore. But if you can tolerate a ketogenic diet, then drink all you want and don't worry about calories.

 

I should also have mentioned eggs, especially free range organic eggs, where the birds aren't fed garbage food tainted with metals and VOCs. Free range also means they're free to graze on grass, which contributes to omega-3 production. This is in contrast to caged grain-fed birds. I wash the shell with dish soap to kill bacteria, then crack it open and drink it raw, at some very small risk of salmonella poisoning, which is generally not life threatening and I've never experienced. Key point: if you notice that the egg tastes like candy (vanilla ice cream, in my case), you've probably become severely choline defficient. The brain is known to radically alter the flavor of otherwise digusting foods in order to encourage intake. This usually occurs in malnourished individuals, but can also happen due to poor absorption or acceleration depletion. Also, note that eggs are loaded with cholesterol. My doctor freaked out when I hit 300 on the ketogenic diet, then calmed down when he ordered a particle size profile and found that it was predominantly large-kernel (benign) LDL. No one should be going on statins to "protect" from egg cholesterol!

 

@mag1: That's exactly the problem. "Alzheimer's" is like "cancer". These are catch-all terms for different diseases. We are not well served by this terminology. The problem is that our diagnostic capabilities are so pathetic that it doesn't often matter, because we can't tell the difference until an autopsy is done. And unlike in the case of cancer, everyone's brain has some degree of every form of Alzheimer's: broken vessels, globs of amyloid and phosphotau, inorganic metal ions, etc. So the best course of action is to attempt to prevent all of these problems, within the limits of risk and money.

 

[mag1]

This must be like a million Christmas days for big pharma!

Just think 1700 pay days!

 

http://www.eurekaler...r-anr011316.php

[resveratrol_guy]

This must be like a million Christmas days for big pharma!

Just think 1700 pay days!

 

http://www.eurekaler...r-anr011316.php

 

That is how they'd "fix" it, wouldn't they? A drug for each epigenetic change. Ha!

 

Seriously, though, this is an interesting article because it at least sounds like APOE4 is basically antipterostilbene, in the sense that it's a "SAD diet mimetic". It sounds like it undoes all the epigenetic flips which occur in response to calorie restriction. Presumably, when combined with an actual SAD diet, the result is vastly premature catastrophe. I wonder what the effect of pterostilbene would be, were it administered in heavy doses to homozygous individuals starting as soon as possible after puberty. It might cancel the effect.

 

But of course, why are we even talking about this? We should just use AAVs or CRISPR to shut down APOE4 expression for good. Where's BioViva...

[ceridwen]

Mary Newport says cold pressed coconut oil is greatly superior to Virgin coconut oil

[mag1]

res, you are just so right about the bottom line being CRISPR.

There has been so many decades of what now could be considered as pointless scientific research.

We cannot afford for this to continue on for yet more centuries.

The War of Cancer would then be a Hundreds year War, as would the War on Alzheimer's etc. .

 

With CRISPR it is not necessary to know what is happening inside the black box: all you need to know

is what genetic variant is causing the problem and then all the complicated steps in between can be ignored.

 

Step 1: CRISPR it,

Step 2: There is no Step 2. Game over.

Step 3: Find out where the party's at.

 

It appears that this idea has already reached those in positions of political leadership.

It now seems inevitable that someone, somewhere is going to try for a moon launch with CRISPR technology.

The benefits that would be derived in terms of allegiance and respect from the disease communities are simply

too large to ignore.

 

Dithering will not be an effective counter-strategy.

We have already reached a genetic inflection point.

 

The technologies that are available at sites such as Ancestry.com, GEDmatch etc. are extraordinarily powerful.

Our family are now actively trying to determine which variant has caused our family's dementia and then contact those in

the family within the last 10 (or more) generations who might have also inherited the variant. If this effort were successful,

no one on this planet would ever be born again with the variant that has caused us such trouble.

 

This exact approach has already been successfully applied in an extended American cancer family totaling 80,000 members.

http://www.ncbi.nlm....ubmed/26683624 

 

The technology to accomplish is already here, so a 21st Century genetic revolution can be launched immediately with or without

a regulatory blessing.

 

In this context needlessly delaying the roll out of CRISPR technology will simply result in greater pressure to use the already

proven approach outlined above.

 

Edited by mag1, 21 January 2016 - 01:28 AM.

[resveratrol_guy]

I completely agree. All I can say is that I think the Bahamas is set to become the best real estate investment of the next decade, and not just for its sunny beaches. It's because Peter Nygaard, egomaniac though he may be, convinced its government to become the world's most friendly toward stem cell and gene therapies. I would be looking there for solutions based on theories developed elsewhere. It will take time. After all, it's a huge shift in demand on their labor pool, but the policies are well designed for a transition in this direction, hopefully resulting not only in a wide array of treatment choices, but in enconomy-of-scale as well. Nygaard's and BioViva's clinics are both being planned there, as I understand it.

To me, CRISPR is an essential element of that economy-of-scale. We don't have time to deal with AAV complications, mild though they may be, because they would just increase the certification costs of the therapist. CRISPR is no-nonsense technology that doesn't mess with the immune system. It's small enough that we might be able to drive it though leaks in the BBB. And more importantly, it was invented by some very creative bacteria who have more experience dealing with DNA infiltration than our best scientists. It has probably been field tested for a hundred million years or more.

 

Having said that, we are getting ahead of ourselves. AAVs are what we almost have right now, presumably just over the horizon. CRISPR has yet to be humanized, at all. Anyone who has news in that vein is encouraged to post a link here or in the Bioscience News section.

Back on the subject of metals, where do you suppose the most dangerous tap water on the planet is flowing? No doubt in some third world hellhole, right? Wrong. In those areas, everyone knows that it's poison. People undertake whatever means they can to avoid drinking it. On the contrary, it's tainted tap water in cities where dangerous contamination is illegal, and the residents therefore assume that such levels are not breached -- places like Flint, Michigan. This video synopsis of the problem could easily be dismissed as a conspiracy documentary, except that it's a CNN news production! In America, we are so often reminded of how government standards for tap water are higher than those for bottled water. I couldn't agree more. And as the officials involved in this affair discovered, the easiest way to enforce standards is to change the records so that the measurements comply. This is science at its finest!
 

[mag1]

At an even higher level of abstraction, it is worthwhile to mention the hidden driver of all of this change: the Singularity force.

All roads in medicine now seem to be heading to CRISPR, yet all the roads from CRISPR now appear headed to the Singularity.

Potentiating a Singularity would have profound implications for Alzheimer's treatment.

 

As mentioned above with current technology even a single person (without access to any external funding) with a family

history of dementia could make extinct a dementia causing variant that probably is causing hardship on a global scale.

People Power!

 

It is surprising that such a concept has not taken hold on a broader scale.

Why not use the same idea outlined above and eliminate disease?

Which is to say all disease, in all people, for all time.

 

This strategy appeared to be successful for the cancer family noted above.

Why not for everyone, everywhere?

 

This would be a moonshot project that could be done on a shoe string budget and would be 

assured of success as it has already been accomplished at a medium scale.

 

Such a project would not need any complex or innovative technology.

Leadership is not only about doing difficult things to prove that they can be done, but also

doing simple things because they need to be done.

 

 

Discussing the desire to manifest a singularity event might be in order (even given the nominal topic of this thread).

 

Clearly we are now approaching a maelstrom of change: a Singularity.           

Yet, many have used their position of power in the community simply to shield themselves against the change that started

in decades and centuries past at a glacial pace and now appears to be rapidly approaching.

 

Even still, we should pledge that we want this change to happen: the sooner the better.

While this might result in a loss of our own personal status, wealth etc., we still want to manifest this change

because of the enormous potential it offers for a better life.

By our firm resolve and organized effort, it is achievable.

 

Perhaps first on the list of priorities is to stop rewarding failure.

Those communities that embrace the approaching singularity should be rewarded. 

Edited by mag1, 21 January 2016 - 06:15 PM.

[mag1]

http://www.ncbi.nlm....pubmed/26775960

 

[niner]

As mentioned above with current technology even a single person (without access to any external funding) with a family

history of dementia could make extinct a dementia causing variant that probably is causing hardship on a global scale.

People Power!

 

How would this work?  Would the single person have to track down every other person with the same variant and kill them so they don't reproduce?  See to it that all further reproduction is done via IVF, CRISPR-edit the error, and re-insert the DNA back into the embryo?  Aren't we a little early in the development of this technology to expect that random people will be doing this without any external funding?  So far, no one has ever done this, even with all the funding in the world.

[Kalliste]

 

resveratrol_guy,

 

I am sorry to bother you, but I believe you have mentioned trying several things with a significant member of your family. My condolences that there has not been a complete solution.

 

Would you post what you have tried, and maybe what you might be currently leaning towards? You mentioned Pterostilbine in another thread, and I am wondering about a good source of bulk powdered U.S. sources?

 

mag1, it is interesting that you are trying the silica water. .

 

Dementia is a catch-all term for many different diseases. What you first need is a diagnosis. I mean, it is "copper AD" or beri beri or TBI or vascular dementia or Parkinson's dementia or a MTHFR mutation or what? There are very different treatments depending on the particular pathology, and a lot of precious time and money can be wasted pursuing inappropriate ones. That said, I take my research advice from scientific publications, not the FDA.

 

If you just want a short list of some of the better treatments which may or may not suit any particular case, I would suggest researching, in no particular order: (1) chelation or zinc supplementation to evict copper, as we've just been discussing here; (2) mesenchymal stem cell therapy; (3) methylcobalamin and methylfolate supplementation; (4) shiitake-maitake extract; (5) ashitaba and ashitaba chalcone; (6) intranasal NGF administration; (7) Curcubrain; (8) LLLT therapy; (9) dark chocolate low in lead and cadmium (e.g. Edangered Species 88%); (10) juices rich in kale (watch kidney effects, and see also the Kame dementia study); and (11) lion's mane mushroom. There are many other novel approaches here on Longecity, as in the Brain Health section.

 

As to Pterostilbene, I recommend Pteropure from Chromadex. They have a very deep auditing process which allows them to know the precise levels of VOC comtamination of each sample. Just be careful: until you learn your dosing limits, be advised that you could actually crash your blood glucose if you take upwards of 200 mg in one dose. It certainly does suppress hunger within an hour or so.

 

 Good list. I would add excess iron accumulation causing ferrotoxicity.

[resveratrol_guy]

Just because I know we all need something to make us even more paranoid about metals exposure, I compiled a list of avoidable exposure routes which in my view may end up being at least as hazardous as lifelong consumption of tap water from copper plumbing. In particular, these routes by their nature defy accurate measurement, which makes them particularly insidious.

1. Handheld can openers, except those which cut horizontally around the outside edge of the top (e.g. Zyliss SafeEdge). Most handheld openers actually leave little flakes of can metal in the contents. I quit using them years ago because I noticed tiny flakes of steel in my soup! I'm suspicious of mechanized can openers as well, for this reason, and also because they tend to produce metal dust, which then migrates to other cans and may get brushed into food.

2. Canned food. Unless the can either has no seam and is lined in either clear plastic or white enamel, I never buy the product again. It seems that whenever I call customer service to let them know that visible seams on the interior are unacceptable in the 21st century, I get the same answer: it's lead-free. First of all, how do they know that? Presumably, they got their cans from the cheapest vendor, who surely wouldn't dream of cheating. Secondly, even if it's free of lead, what metals are actually in it? Why even debate this? Switch brands.

3. Foods packaged in foil or foil-backed paper. Especially in the latter case, the foil tends to flake apart during unwrapping, producing tiny flecks of the stuff which actually contain physiologically significant amounts of aluminum. If you're not very careful, they can end up in your food. This is a particularly challenging problem because the flakes tend to mirror the food around them, which allows them to escape visual inspection.

 

4. Supplement containers with foil seals under the plastic top. Inevitably, you never quite manage to get all the foil off the top. Then, every time you close the top, it rips up the foil around the edge a bit more. Over time, flakes get into the container, and may take a ride on one of the pills into your body. Why is it that billion-dollar health supplement companies still haven't realized this obvious problem?

5. Mercury fillings, but not because of their own leaching of mercury. As someone who had small ones for many years, I recall how aluminum foil would set them off in sort of an electric shock. This is due, in fact, to an electron current resulting from the foil reducing the silver-mercury amalgam to produce free mercury. But over the years, I discovered that aluminum foil was not the only problem: simple stainless steel utensils would set off the current as well, albeit not so fiercely. The point is that such oxidation-reduction reactions might enhance the rate of mercury transport into the body. The obvious answer is to have the fillings removed. However, doing so requires a competent specialist using a vaccuum pump, very frequent oral suction, and dedicated oxygen supplies for both dentist and patient. (I'm not joking. I had this done myself.) You also need to try to avoid swallowing the debris, and ideally should have a stomach loaded with tumeric, chocolate, or some powerful chelating food such as cilantro.
 

Sorry for the OCD rant. But I think the exposure via these routes is probably significant in light of the dementia hazards, so go buy some vegetables and make your life better.

 

Edited by resveratrol_guy, 23 January 2016 - 04:21 PM.

[resveratrol_guy]

http://www.ncbi.nlm....pubmed/26775960

 

While I don't endorse alpha-tocopherol consumption, it sounds like we need lipidated EGCG. And to anyone who actually tries it, please don't use a sonicator, on account of the localized thermal spikes.

 

Realistically, this sounds like a job for Verdure Sciences or Anthony Loera's outfit. But I would bet that it's pay dirt.

 

Hey niner, do you think you could pull this off in your own kitchen/lab with MCT oil or something?

 

Edited by resveratrol_guy, 23 January 2016 - 04:46 PM.

[mag1]

Might someone with adult computer privileges relocate my posts and the responses to my posts to a new Alzheimer's thread?

Before this were to be done, what would the others who have made responding posts think of this idea?

 

I have just looked back before most of my posts starting around page 14 of this thread and there were so many thoughtful intelligent

posts made by a variety of posters. It appears that this diverse group of posters has been displaced by one loud mouth ... ME.

 

Some kids on the thread want to mosh out with their heavy metal, while others on the thread are into a more sedate,

tea drinking classical music style. Viva la difference! 

 

Time for a new AD thread, anyone?

Edited by mag1, 23 January 2016 - 09:09 PM.

[mag1]

In for a penny in for a pound...

 

This is just so terrifying! We have not discussed BMAA enough on this thread or the forum.

Protein mimics sound so scary!

 

http://www.ncbi.nlm....pubmed/24374297

 

I just got a truck load of oysters from Caloosahatchee. Anyone want them?

http://www.ncbi.nlm....5?log$=activity

 

I would sure be in for an Indiegogo campaign that created a gene drive that rid this planet of BMAA producing cyanobacteria.

Anyone? 

 

{Ew, looks like virtually all cyanobacteria produce BMAA. Not sure whether ridding the entire planet of cyanobacteria would be such

a good plan. Life on this planet arose due to the oxygen made by cyanobacteria.} 

Edited by mag1, 24 January 2016 - 12:01 AM.

[mag1]

Here is the url again.

The below article was able to comply an extended family tree for 80,000 that had a cancer causing variant.

As noted in the article, genetic counseling would be a helpful strategy to reduce the frequency of the variant in the future.

 

Such a strategy would be helpful for many other families coping with genetically determined illnesses.

A genetic revolution can now occur without any additional technologies needed.

 

Once the variant of interest is located in our family such a strategy would be used.

The freely accessible genetic databases provide us with overwhelming power to achieve such a result.

Anyone else with a genetic issue could do likewise.

 

We have already crossed the line into a profoundly different genetically selected world. 

 

http://www.ncbi.nlm....pubmed/26683624

[resveratrol_guy]

Here is the url again.

The below article was able to comply an extended family tree for 80,000 that had a cancer causing variant.

As noted in the article, genetic counseling would be a helpful strategy to reduce the frequency of the variant in the future.

 

Such a strategy would be helpful for many other families coping with genetically determined illnesses.

A genetic revolution can now occur without any additional technologies needed.

 

Once the variant of interest is located in our family such a strategy would be used.

The freely accessible genetic databases provide us with overwhelming power to achieve such a result.

Anyone else with a genetic issue could do likewise.

 

We have already crossed the line into a profoundly different genetically selected world. 

 

http://www.ncbi.nlm....pubmed/26683624

 

This sounds like Sergey Brin's idea in 2010. His wife was the CEO of 23andMe. Then the FDA "protected" us by shutting down genetic testing. So your idea, while sensible, is currently unimplementable in the US. (Bahamas, anyone?)

[mag1]

No we are all go to move this ahead.

We already have an exome sequence for our loved one.

It is no longer necessary to do more exome sequencing.

 

All we need to do is find other relatives with dementia and narrow down the search space.

This should not be very difficult.

 

When you have somewhat distant relatives, they only share a fairly small segment of DNA with you.

Once the variant containing segment has been found, then all you need is matching haplotypes for other relatives which can be

found by simply looking at gene chip results.

 

This was all demonstrated in the above url.

For the 80,000 person family tree, they only bothered to sequence a few exomes.

 

A genetic revolution can now begin based merely on selection.

Without publicly accessible family trees, gene chips and exome sequencing this could not and did not happen.

Now that everything has fallen into place, a transformative genetic revolution can begin.

 

There are no obvious ways for regulators to regulate this out of existence.

Edited by mag1, 26 January 2016 - 02:42 AM.

[niner]

 

Here is the url again.

The below article was able to comply an extended family tree for 80,000 that had a cancer causing variant.

As noted in the article, genetic counseling would be a helpful strategy to reduce the frequency of the variant in the future.

 

Such a strategy would be helpful for many other families coping with genetically determined illnesses.

A genetic revolution can now occur without any additional technologies needed.

 

Once the variant of interest is located in our family such a strategy would be used.

The freely accessible genetic databases provide us with overwhelming power to achieve such a result.

Anyone else with a genetic issue could do likewise.

 

We have already crossed the line into a profoundly different genetically selected world. 

 

http://www.ncbi.nlm....pubmed/26683624

 

This sounds like Sergey Brin's idea in 2010. His wife was the CEO of 23andMe. Then the FDA "protected" us by shutting down genetic testing. So your idea, while sensible, is currently unimplementable in the US. (Bahamas, anyone?)

 

It looks like Brin just issued an open call for Parkinson's patients, but I don't think they went back genealogically.  If they did use a genealogical approach, they might be able to collect more patients, particularly those with the LRRK mutation but without symptomatic Parkinson's. 

 

The FDA never shut down genetic testing, and 23andMe continued to test without interruption.  The FDA's beef with 23andMe was about health claims, particularly when they started advertising on television.  For a while, 23andMe didn't do any analysis of the data they generated, but you could download your data and take it to third party analysis sites or do it yourself.  23andMe has worked with FDA and now provides some level of analysis again.  They continue to run their program of gathering health information from people they have SNP data on.

[mag1]

There have been ongoing sensitivities about DNA testing.

It was not that many years ago that getting an APOE epsilon genotype was not especially easy.

23andme only were able to overcome their "technical challenges" with APEO epsilon 4 a few years ago.

 

Surprisingly APOE genotyping appears to still be a hurdle to overcome even in 2016.

http://www.health.ha...&utm_content=pr

 

{BTW does anyone know of the current legal status of exome sequencing in Europe.

I thought that there might have been some consideration given to restricting access.}

Edited by mag1, 26 January 2016 - 02:54 AM.

[resveratrol_guy]

It looks like Brin just issued an open call for Parkinson's patients, but I don't think they went back genealogically.  If they did use a genealogical approach, they might be able to collect more patients, particularly those with the LRRK mutation but without symptomatic Parkinson's. 

 

The FDA never shut down genetic testing, and 23andMe continued to test without interruption.  The FDA's beef with 23andMe was about health claims, particularly when they started advertising on television.  For a while, 23andMe didn't do any analysis of the data they generated, but you could download your data and take it to third party analysis sites or do it yourself.  23andMe has worked with FDA and now provides some level of analysis again.  They continue to run their program of gathering health information from people they have SNP data on.

 

Right, Brin was advocating the search for genetic cause-and-effect on a massive scale such as that provided by 23andMe, not geneaological data gathering specifically; the 23andMe approach would involve a much larger data set, of course. Although his initial focus was on Parkinson's, the same technique could apply to almost any genetic propensity.

 

"They continue to run their program of gathering health information from people they have SNP data on" -- exactly; but that's not testing; it's data mining. ("Updating to the current platform is presently unavailable," says their website.)

 

On another topic, what do you think of liposomal EGCG (see above)?

[mag1]

Sulfide, wasn't this talked about before on the thread?

 

http://patents.com/us-9242009.html

 

 

Anyone know what ever happened to suspended animation with H₂S?

That could have very substantial medical applications.

 

http://www.longecity...talk-mark-roth/

Edited by mag1, 27 January 2016 - 05:40 PM.

[Avatar of Horus]

A recent paper of a discovery about the similarity of laminopathies and age-related progressive neurodegenerative disorders:

Lamin Dysfunction Mediates Neurodegeneration in Tauopathies

Frost B, Bardai FH, Feany MB

Curr Biol. 2016 Jan 11

http://www.ncbi.nlm....pubmed/26725200

Abstract

The filamentous meshwork formed by the lamin nucleoskeleton provides a scaffold for the anchoring of highly condensed heterochromatic DNA to the nuclear envelope, thereby establishing the three-dimensional architecture of the genome [1]. Insight into the importance of lamins to cellular viability can be gleaned from laminopathies, severe disorders caused by mutations in genes encoding lamins. A cellular consequence of lamin dysfunction in laminopathies is relaxation of heterochromatic DNA [1]. Similarly, we have recently reported the widespread relaxation of heterochromatin in tauopathies [1]: age-related progressive neurodegenerative disorders, including Alzheimer's disease, that are pathologically characterized by aggregates of phosphorylated tau protein in the brain [2, 3]. Here we demonstrate that acquired lamin misregulation though aberrant cytoskeletal-nucleoskeletal coupling promotes relaxation of heterochromatin and neuronal death in an in vivo model of neurodegenerative tauopathy. Genetic manipulation of lamin function significantly modifies neurodegeneration in vivo, demonstrating that lamin pathology plays a causal role in tau-mediated neurotoxicity. We show that lamin dysfunction is conserved in human tauopathy, as super-resolution microscopy reveals a significantly disrupted nuclear lamina in postmortem tissue from human Alzheimer's disease brain. Our study provides strong evidence that tauopathies are neurodegenerative laminopathies and identifies a new pathway mediating neuronal death in currently untreatable human neurodegenerative disorders, including Alzheimer's disease.

 

[resveratrol_guy]

 

A recent paper of a discovery about the similarity of laminopathies and age-related progressive neurodegenerative disorders:

Lamin Dysfunction Mediates Neurodegeneration in Tauopathies

Frost B, Bardai FH, Feany MB

Curr Biol. 2016 Jan 11

http://www.ncbi.nlm....pubmed/26725200

Abstract

The filamentous meshwork formed by the lamin nucleoskeleton provides a scaffold for the anchoring of highly condensed heterochromatic DNA to the nuclear envelope, thereby establishing the three-dimensional architecture of the genome [1]. Insight into the importance of lamins to cellular viability can be gleaned from laminopathies, severe disorders caused by mutations in genes encoding lamins. A cellular consequence of lamin dysfunction in laminopathies is relaxation of heterochromatic DNA [1]. Similarly, we have recently reported the widespread relaxation of heterochromatin in tauopathies [1]: age-related progressive neurodegenerative disorders, including Alzheimer's disease, that are pathologically characterized by aggregates of phosphorylated tau protein in the brain [2, 3]. Here we demonstrate that acquired lamin misregulation though aberrant cytoskeletal-nucleoskeletal coupling promotes relaxation of heterochromatin and neuronal death in an in vivo model of neurodegenerative tauopathy. Genetic manipulation of lamin function significantly modifies neurodegeneration in vivo, demonstrating that lamin pathology plays a causal role in tau-mediated neurotoxicity. We show that lamin dysfunction is conserved in human tauopathy, as super-resolution microscopy reveals a significantly disrupted nuclear lamina in postmortem tissue from human Alzheimer's disease brain. Our study provides strong evidence that tauopathies are neurodegenerative laminopathies and identifies a new pathway mediating neuronal death in currently untreatable human neurodegenerative disorders, including Alzheimer's disease.

 

 

Interesting... but do you have any clue what to do to prevent this? Would HDAC inhibitors help to keep the DNA archored to the nuclear envelope, by virtue of not unfurling so readily?
 

[mag1]

res, you are onto something with the lipo EGCG idea.

Many known beneficial chemicals have bad bioavailability.

 

Seems you really can't avoid metals unless you were to live out in a shack somewhere.

Arsenic anyone?

http://www.naturalne...rsenic_FDA.html

 

Edited by mag1, 30 January 2016 - 02:07 AM.

[niner]

Arsenic anyone?

http://www.naturalne...rsenic_FDA.html

 

Natural News is about as close as you can come to a contrary indicator.  In other words, whatever they say, the opposite is probably closer to the truth.

[mag1]

That's probably about right, I just pulled out the first url from the search.

I had heard this story from somewhere else (that I am now unable to find).

 

Here's the FDA link.

http://www.fda.gov/A...n/ucm257540.htm

Edited by mag1, 30 January 2016 - 04:36 AM.

[Logic]

res, you are onto something with the lipo EGCG idea.

Many known beneficial chemicals have bad bioavailability.

 

Seems you really can't avoid metals unless you were to live out in a shack somewhere.

Arsenic anyone?

http://www.naturalne...rsenic_FDA.html

 

Green tea is good for you, but only if drunk in moderation. While the polyphenols in green tea are credited with preventing heart disease and cancer, it seems they can cause liver and kidney damage if consumed in very large quantities, a review of studies into the toxicity of polyphenols has shown.

"People shouldn't be too alarmed by this, but those taking supplements may experience problems," says lead author Chung Yang of Rutgers, the State University of New Jersey.
He stresses that up to 10 small cups of green tea a day is fine. Problems are likely in people who take supplements, which can contain up to 50 times as much polyphenol as a single cup of tea.

Yang's review cites experiments in which rodents and dogs died from liver poisoning when given very large doses of polyphenols. He also reports cases of people with liver toxicity after overdosing on green-tea-based supplements. Their symptoms disappeared when they stopped taking the pills, only to return when they started taking them again (Chemical Research in Toxicology, vol 20, p 583).

http://www.longecity...ea-supplements/

[mag1]

Hmm, wonder whether repurposing for AD would make any sense.

Human clinical phase 1 trial for CuATSM starts in April for ALS.

 

"we treated these pups with the PET-imaging agent CuATSM, which is known to deliver copper into the CNS within minutes."

 

http://www.ncbi.nlm....pubmed/26826269

http://www.alzforum....rescue-als-mice

 

The copper problem in clinical AD relates to a deficiency of protein bound copper in the right places of the brain.

 

"For these pathologies, copper bound to proteins is able to protect against free radicals by reduction from cupric Cu++ to cupreous Cu+. We have previously demonstrated in bovine brain homogenate that free radicals produce proteinase K-resistant prion after manganese is substituted for copper. Since low brain copper levels have been described in transmissible spongiform encephalopathies, in substantia nigra in Parkinson's disease, and in various brain regions in AD, LBD, and CJD,

 

http://www.ncbi.nlm....pubmed/25125459

 

Might CuATSM  get the copper to the right place in the right form?

 

 

Efforts for this in Parkinson's also

 

"They found that an organic molecule containing copper, Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone), or Cu-ATSM, blocked both nitration and oligomerization of α-synuclein.

... In all four models, the copper-containing molecule prevented dopaminergic neuron death and improved dopamine metabolism,"

 

http://www.alzforum....atments-horizon

 

Not sure if there has been any recent developments for this idea in PD patients.

 

 

 

 

 

Edited by mag1, 06 February 2016 - 06:20 PM.

[mag1]

Interesting, looks like Cu II(atsm) has been investigated in AD.

7 years ago?

The above quote noted that Cu II (atsm) is already used in PET scans.

Could go off lablel.

 

"glyoxalbis(N(4)methylthiosemicarbazonato)Cu^II (Cu^II (gtsm)) restored intracellular copper levels, decreased insoluble A[beta] levels and improved cognition"

http://www.ncbi.nlm..../?term=19122148

 

Only difference between Cu^II (gtsm) and Cu^II (atsm) is a double methyl substitution for the top Hydrogen.