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Alzheimer's protein identified, possible future vaccine or even cure.
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olePigeon
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Feb 3, 2012, 01:46 PM
 
http://www.nytimes.com/2012/02/02/he...pagewanted=all

Pretty exciting. The protein (Tau) has been identified as the cause and spread of Alzheimer's. The mutated version causes the parts of the brain to die. Now that it's been identified, scientists can move forward into possibly creating a vaccine and even cure for Alzheimer's. It is also possible that other degenerative diseases such as Parkinson's may work in a similar way.
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Waragainstsleep
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Feb 3, 2012, 02:26 PM
 
This is certainly a big step. Good news indeed.
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Uncle Skeleton
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Feb 3, 2012, 09:25 PM
 
This doesn't exactly suggest a treatment strategy, least of all a vaccine. You don't vaccinate against proteins (rather than pathogens), and you certainly don't want to do it when the protein is made by the very cells you're trying to protect.

This is an unexpected finding, scientifically, but I don't think it has many implications medically. Tau is not a new discovery, the new part is only the possibility that it travels around the brain so far as this result implies.
     
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Feb 4, 2012, 11:06 AM
 
At least once you know the mechanism you can start looking for ways to stop it.
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Feb 4, 2012, 12:07 PM
 
I think it's gigantic leap to say they can now develop a vaccine (or treatment). It's fantastic news that they've isolated this mutated protein and its behavior, but that's really as far as it goes. I hold out hope that this does, in fact, lead to some form of treatment or cure down the road. Sadly, I know it will come far too late to benefit my mother. She's too far down the Alzheimer's road, I'm afraid.
     
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Feb 4, 2012, 12:29 PM
 
It was found in mice, not men. There is more questioning today of how accurate the results transfer over.
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Waragainstsleep
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Feb 4, 2012, 12:53 PM
 
Yes but this time the mice brains were producing human proteins so it should be pretty close.
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Uncle Skeleton
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Feb 4, 2012, 02:10 PM
 
No not really. That's like saying a Mac program's binary will do the same thing running on Linux as it would on Mac. The behavior of the programtein depends heavily on its environment.
     
Person Man
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Feb 4, 2012, 03:43 PM
 
Originally Posted by Uncle Skeleton View Post
This doesn't exactly suggest a treatment strategy, least of all a vaccine. You don't vaccinate against proteins (rather than pathogens), and you certainly don't want to do it when the protein is made by the very cells you're trying to protect.

This is an unexpected finding, scientifically, but I don't think it has many implications medically. Tau is not a new discovery, the new part is only the possibility that it travels around the brain so far as this result implies.
Actually, if you read the article, it most certainly *does* suggest a treatment strategy. A vaccine isn't the right word for it, though. The article mentions that an antibody to the tau protein could be developed.
     
Waragainstsleep
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Feb 4, 2012, 04:14 PM
 
Originally Posted by Uncle Skeleton View Post
No not really. That's like saying a Mac program's binary will do the same thing running on Linux as it would on Mac. The behavior of the programtein depends heavily on its environment.
I can see how your points would relate to this if they were at the stage of testing an antidote in mice, but since the observations of the proteins behaviour in the mice seem to match the development of Alzheimers quite closely in humans it seems probable that they have found the correct mechanism that they should be trying to stop.
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Uncle Skeleton
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Feb 4, 2012, 04:33 PM
 
Originally Posted by Person Man View Post
Actually, if you read the article, it most certainly *does* suggest a treatment strategy. A vaccine isn't the right word for it, though. The article mentions that an antibody to the tau protein could be developed.
Tau antibodies as an alzheimers treatment isn't new though. For example, here's a paper from a year ago that already did exactly that (meaning we didn't need to know this new information in order to pursue the antibody therapy approach)

http://www.google.com/url?sa=t&rct=j...QI8zgYGdvBDygg
(don't know if that link will work, so: here is another)

BTW, I'm not all doom and gloom. I was pretty excited about this surprising result:

Reversal Of Alzheimer's Symptoms Within Minutes In Human Study
     
Uncle Skeleton
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Feb 4, 2012, 04:47 PM
 
Originally Posted by Waragainstsleep View Post
I can see how your points would relate to this if they were at the stage of testing an antidote in mice, but since the observations of the proteins behaviour in the mice seem to match the development of Alzheimers quite closely in humans it seems probable that they have found the correct mechanism that they should be trying to stop.
Unfortunately, it's not that simple. All they showed is that tau (neurofibrillary tangles) spread in a similar way to humans, but they didn't show that these cause cell death, nor even that they are associated with cell death (the model animals didn't have neuron death, at least none was reported. I am eagerly awaiting the release of the Neuron article also mentioned by NYT). Some protein aggregates that were originally thought to cause disease, are actually a side-effect of the body's defense against the disease. Here was a very elegant demonstration of one such circumstance:

Study Using Robotic Microscope Shows How Mutant Huntington's Disease Protein Affects Neurons: National Institute of Neurological Disorders and Stroke (NINDS)

They tracked individual Huntington's disease neurons (a 100% genetic disorder) and found that the individual cells that developed plaques were actually the ones that survived the longest, and often the ones that died never got any plaques at all.
( Last edited by Uncle Skeleton; Feb 4, 2012 at 09:04 PM. )
     
Waragainstsleep
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Feb 4, 2012, 05:53 PM
 
Fascinating. I guess the article is oversimplifying things a little.
I take it nothing further has panned out yet from the 2008 article you posted about perispinal etanercept?
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ghporter
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Feb 4, 2012, 08:59 PM
 
While symptoms may be reversed, in most cases the adult brain does not "heal" in a way that restores structures which have been physically damaged. At best, current sufferers may be stabilized and their more acute symptoms reversed to some extent. What must be understood by everyone is that for a treatment to be useful, it must be employed before significant symptoms develop, which requires identifying the faulty gene in unaffected people and starting treatment immediately to prevent the damage.

Further, most lay people think of all dementia as "Alzheimer's Disease," when that is hardly the case. Far more individuals suffer from vascular dementia, Parkinsonian dementia, ischemic dementia and countless other well identified types of dementia. Each mechanism of injury has subtly different effects and presentations.

The Alzheimer's Association states that 60-80% of dementia cases are diagnosed as Alzheimer's type, but for decades the ONLY way to verify that diagnosis was post-mortem microscopic examination of the brain, which has never been a common step. It is also not uncommon for multiple types of dementia to manifest in the same person; vascular and ischemic dementia on top of Alzheimer's dementia is a very unpleasant mix which I happened to encounter just yesterday. Point: this is a Very Good Thing, but it is not a "cure for dementia." It is, rather, a potential means to block the progress of the most commonly diagnosed type of dementia.

Sorry if that all sounds pretty bleak, but when you have to call someone and tell him "your mother is not able to participate in therapy because she cannot follow the simplest functional instructions such as 'touch your nose,' and she will, unfortunately, continue to require total care including being fed each bite," it makes you hesitant to celebrate what at best would help people who are not yet noticeably impaired avoid becoming so.

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Feb 4, 2012, 09:22 PM
 
Originally Posted by Waragainstsleep View Post
I take it nothing further has panned out yet from the 2008 article you posted about perispinal etanercept?
I don't know. I tried to see if something else has been published since, but I couldn't find it. At the time, the result was so striking that most people assumed it was somehow an error, and would later be disproved. I'm an optimist, and hold out hope that it's real until it gets disproved, and as far as I can tell the disproving hasn't happened. It might just be because any experiment using human subjects entails years of delays and red tape, and the follow up might be just around the corner. But my best guess is just like what Glenn says: that type of recovery simply shouldn't be possible, given what we know about the pathology. So while I give it the benefit of the doubt, I wouldn't be surprised at all if this treatment is never heard from again, due to it having been an illusion in the first place My guess is that 4 years is long enough to expand on the last experiment, and if a confirmation was coming we would have seen it by now

The neurons are dead (we believe), and no molecular drug can replace them. Neurons don't naturally regenerate, at least not in the numbers or locations required, so without providing a cell transplant, you can't ever expect to reverse the symptoms, only to halt or slow the decline. Even if we're wrong about the cells dying, like for example if they stopped being neurons or stopped being the right kind of neuron (which might explain why histology sees them as gone), for the cells to switch back would surely take more than the mere hours that this result showed.
( Last edited by Uncle Skeleton; Feb 4, 2012 at 10:17 PM. )
     
Athens
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Feb 9, 2012, 03:17 PM
 
Originally Posted by ghporter View Post
While symptoms may be reversed, in most cases the adult brain does not "heal" in a way that restores structures which have been physically damaged. At best, current sufferers may be stabilized and their more acute symptoms reversed to some extent. What must be understood by everyone is that for a treatment to be useful, it must be employed before significant symptoms develop, which requires identifying the faulty gene in unaffected people and starting treatment immediately to prevent the damage.

Further, most lay people think of all dementia as "Alzheimer's Disease," when that is hardly the case. Far more individuals suffer from vascular dementia, Parkinsonian dementia, ischemic dementia and countless other well identified types of dementia. Each mechanism of injury has subtly different effects and presentations.

The Alzheimer's Association states that 60-80% of dementia cases are diagnosed as Alzheimer's type, but for decades the ONLY way to verify that diagnosis was post-mortem microscopic examination of the brain, which has never been a common step. It is also not uncommon for multiple types of dementia to manifest in the same person; vascular and ischemic dementia on top of Alzheimer's dementia is a very unpleasant mix which I happened to encounter just yesterday. Point: this is a Very Good Thing, but it is not a "cure for dementia." It is, rather, a potential means to block the progress of the most commonly diagnosed type of dementia.

Sorry if that all sounds pretty bleak, but when you have to call someone and tell him "your mother is not able to participate in therapy because she cannot follow the simplest functional instructions such as 'touch your nose,' and she will, unfortunately, continue to require total care including being fed each bite," it makes you hesitant to celebrate what at best would help people who are not yet noticeably impaired avoid becoming so.
Research in stem cell's might one day provide a method to repair damage to the brain though. If the damage can be stopped with one kind of treatment, there is always hope a different type of treatment could repair some or all the physical damage.
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Feb 10, 2012, 07:40 AM
 
Physical damage to the brain involves both biological and neurological issues. While rebuilding neurons may eventually be possible, the connections between those neurons is not biological, it's experience-based and develops over the lifetime. More healthy neurons would be good, but you cannot rebuild lost memory, lost skills, etc. If it were some other organ, that would be different, but the brain is just too complicated, and the damage starts so quietly and so long before any signs are evident, that repairing just the neurons themselves would be of limited assistance.

Working with Alzheimer's patients on a regular basis, I can assure you that it is way more than the amount of healthy brain cells involved, and the impact of the subtle changes to a person adds up. I wholeheartedly wish that there were a reasonable chance that the brains of these poor people could be fixed. But that's not how the brain works...

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Feb 10, 2012, 10:22 AM
 
Originally Posted by Athens View Post
Research in stem cell's might one day provide a method to repair damage to the brain though.
I have a theory on how to help accelerate stem cell research (and approval): If someone can find a way to turn stem cells into erectile tissue, most of the protests and complaints and ethical questions should evaporate pretty fast.
I have plenty of more important things to do, if only I could bring myself to do them....
     
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Feb 10, 2012, 11:28 AM
 
Glenn that's a assumption. To date we have never been able to regenerate brain cells so we don't know how new cells would react. I said physical damage for a reason. I know nothing can bring back memories but te ability to restore the ability to make new memories and for the brain to adapt with new brain cells is unknown. The brain is amazing and so is its ability to compensate. Children that have lost up to half the brain ended up adapting with the other half. This isn't the same for adults but with stem cell research who knows what new brain cells can do. I am optimistic. But Im a realist. I understand that even with new cells nothing could change for a person too. We just don't know.
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reader50
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Feb 10, 2012, 01:41 PM
 
Perhaps my info is out of date, but isn't long-term memory still believed to be chemical in nature? If so, replacing neurons in damaged areas might allow the I/O drivers to be rebuilt.
     
olePigeon  (op)
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Feb 10, 2012, 01:51 PM
 
Originally Posted by ghporter View Post
Physical damage to the brain involves both biological and neurological issues. While rebuilding neurons may eventually be possible, the connections between those neurons is not biological, it's experience-based and develops over the lifetime. More healthy neurons would be good, but you cannot rebuild lost memory, lost skills, etc. If it were some other organ, that would be different, but the brain is just too complicated, and the damage starts so quietly and so long before any signs are evident, that repairing just the neurons themselves would be of limited assistance...
I had a classmate in college that was in her early 60s. She had just started college again for the second time in her life, but she doesn't remember anything about the first time. She had gotten in a horrible car accident and some shrapnel went into her brain, then she was in a coma for a few months. At first they thought her brain was damaged irreparably, and that her memory area had been damaged (like the movie Memento.) After a few years they figured out it was trauma induced amnesia, and while she got her capability to remember back, she had none of her former memories. She had to relearn everything at the age of 40. Went from kindergarten and finally through college by age 60.
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Feb 10, 2012, 02:29 PM
 
Originally Posted by reader50 View Post
Perhaps my info is out of date, but isn't long-term memory still believed to be chemical in nature? If so, replacing neurons in damaged areas might allow the I/O drivers to be rebuilt.
All biology is just a sub-set of chemistry, and all chemistry is just a sub-set of physics (and some say all physics is just a sub-set of mathematics). To the extent that memories are stored chemically, that chemistry takes place inside neurons. If the neurons in question die, the chemistry in question dies with them, or at the very least would become inaccessible.

It may be possible to repurpose surviving neurons to start holding memories, instead of whatever they were doing before. Failing that it may be possible to transplant new neurons and make them start holding memories. Failing that it may be possible to incorporate technology with neurons and store the memories digitally but access them biologically. Or it may be possible to transfer one's entire personality and memory to an artificial brain, and do away with the neurobiology altogether. None of these will revive lost memories.... unless you go the route of the Caprica show, where they simulate memories and personality retroactively by farming the internet...

Maybe people with failing memories should all wear a medallion that automatically records everything they do throughout the day. Not only would it jog their memory, it could be used to reconstruct an artificial brain for them after their bio-brain is totaled. The sooner they start recording, the further back they'll be able to go once the technology is ready. This movie takes it one step further even: Freeze Frame (2004) - IMDb
     
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Feb 10, 2012, 02:34 PM
 
Originally Posted by Athens View Post
To date we have never been able to regenerate brain cells so we don't know how new cells would react.
Actually there have been successful cases where embryonic brain cells have been implanted into Parkinson's patients, and then years later when the patient finally dies, the transplanted neurons were found to still be alive. (More often than not, they weren't, IOW it didn't work, but my point is that on occasion it did work). So we do have at least some idea how new cells would react to being inserted into the niche of lost cells.
     
Waragainstsleep
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Feb 10, 2012, 04:31 PM
 
Originally Posted by Uncle Skeleton View Post
unless you go the route of the Caprica show, where they simulate memories and personality retroactively by farming the internet...
I really loved this idea. I think its pretty feasible too.
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jmiddel
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Feb 10, 2012, 05:34 PM
 
Use promotes neurogenesis. If we could stop the neuronal destruction, simply being active and exercising the brain will cause new neurons to sprout, including in the hippocampus, where it seems that the destruction begins.
     
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Feb 10, 2012, 08:22 PM
 
Originally Posted by Waragainstsleep View Post
I really loved this idea. I think its pretty feasible too.
But isn't it kind of like "living on" through a clone? The clone might be a perfect copy (optimistically), but what good does it to me if my clone gets to live my life? I want to live that life, not him.

If they could create a turing machine so that someone standing right in front of it couldn't tell the difference between me and it, so that I could safely be eliminated and the machine could perform my functions ad infinitum, I consider that a bad thing, not a good one
     
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Feb 10, 2012, 08:30 PM
 
Originally Posted by jmiddel View Post
Use promotes neurogenesis. If we could stop the neuronal destruction, simply being active and exercising the brain will cause new neurons to sprout, including in the hippocampus, where it seems that the destruction begins.
This is far from established. By and large, neurogenesis doesn't exist in the adult mammalian brain. The hippocampus is one VERY rare exception, and it has been shown that in mice (couch potato model) so-called "intellectual enrichment" (running wheel) increases the amount of neurogenesis, it hasn't been shown whether the newly born neurons integrate in the circuit or even whether they stay alive. They undoubtedly have some purpose, but that might have nothing to do with consciousness. The brain does a million things besides consciousness, as evidenced by the similarities between our brains and animals that don't even have consciousness (like arguably, mice). This aside from the fundamental problems of whether a mouse is an adequate model for a human and whether a caged mouse is an adequate model for a free mouse. Lastly, it's pretty clear that the new neurons most likely don't leave the hippocampus, and while the hippocampus is one of the most important structures for memory, the tissue damage evident in Alzheimers is widespread throughout the rest of the cortex. So most likely, even if there is a miracle cure for the hippocampus, all the damage from elsewhere will still be disease-relevant in some way.
     
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Feb 11, 2012, 07:26 AM
 
Originally Posted by Uncle Skeleton View Post
But isn't it kind of like "living on" through a clone? The clone might be a perfect copy (optimistically), but what good does it to me if my clone gets to live my life? I want to live that life, not him.

If they could create a turing machine so that someone standing right in front of it couldn't tell the difference between me and it, so that I could safely be eliminated and the machine could perform my functions ad infinitum, I consider that a bad thing, not a good one
Oh absolutely, your digital replacement wouldn't really be you at all, just a best estimate or simulation of you extrapolated from your medical records, shopping history, FacBook profile and presumably some fairly nifty psychoanalysis software. A digital clone. I think it would be more for your loved ones than anything else though again I'm not sure that would be tremendously healthy. Caprica covered this at the very start when real Zoe was trying to teach CyberZoe how to be more like her in the decisions she made and reactions she had. It then went on to explore the relationships between the family and the digital clone.

I didn't say it was a good idea, just that I liked it.

Of course, you start getting a bit existential if you really delve into it. Its like on Star Trek with the transporters. Once you go through one, is it you that comes out the other side? It destroys you at one end and builds a new you from new atoms at the other. It would be the perfect scientific experiment to test for the presence of a soul. Kindof.
Same applies here, if the approximation of you is good enough, maybe your consciousness is ethereally connected to a certain combination of thought patterns and it doesn't matter where those patterns are running.
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Feb 11, 2012, 09:45 AM
 
Originally Posted by Athens View Post
Glenn that's a assumption. To date we have never been able to regenerate brain cells so we don't know how new cells would react. I said physical damage for a reason. I know nothing can bring back memories but te ability to restore the ability to make new memories and for the brain to adapt with new brain cells is unknown. The brain is amazing and so is its ability to compensate. Children that have lost up to half the brain ended up adapting with the other half. This isn't the same for adults but with stem cell research who knows what new brain cells can do. I am optimistic. But Im a realist. I understand that even with new cells nothing could change for a person too. We just don't know.
We DO know that when damage happens to an otherwise healthy brain that some of the connections, whether for motor control, sensation, or memory, are permanently destroyed. With young children whose brains are still developing, those deficits can be overcome by building new connections, but the memories are forever gone. Memory is a vastly complex process, and through decades of study and research into recovery from stroke and traumatic brain injury, memory has been the only thing that has not been recovered, because memory is the specific set of connections among specific neurons, not just connections between a fairly general area and a finger or a leg. I've worked with stroke survivors who were able to learn to use once flaccid legs, but the memories they lost are gone forever. Personality is also like memory, and is permanently altered by damage to the brain; a person with a traumatic brain injury is ALWAYS a "different person" afterward, though there are practices and techniques that help them reproduce their former selves (think Gabby Giffords), or at least simulate that person they once were as seen by others.

Sadly, we DO know. Fixing a brain is a slow and tortuous process, and it is never perfect,

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Feb 11, 2012, 03:43 PM
 
Originally Posted by Waragainstsleep View Post
Of course, you start getting a bit existential if you really delve into it. Its like on Star Trek with the transporters. Once you go through one, is it you that comes out the other side? It destroys you at one end and builds a new you from new atoms at the other.
I like how they treated it in The Prestige.

     
   
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