24 ms·

Chemical clears Alzheimer's protein and restores memory in mice

452 points by coris47 11y ago

keeptrying 11y ago
There have been at least 3 previous solutions for AD in mice which have never panned out in humans.
- brwnll 11y ago
  Source?
  - pcrh 11y ago
    Actually its more like 300 treatments that haven't panned-out... ‘Too much good news’ – are Alzheimer mouse models trying to tell us how to prevent, not cure, Alzheimer’s disease? https://www.ncbi.nlm.nih.gov/pubmed/?term=20542579 https://www.ncbi.nlm.nih.gov/pubmed/?term=20542579
plg 11y ago
it's a great day for mouse health
- wiremine 11y ago
  You say that tongue in cheek, but as a non-scientist, I've always wondered how much "mouse science" ultimately translates to humans. My guess is it's very low, but knowing a percentage would help me better understand how to proceed reports like this.
  - moioci 11y ago
    Not all that low: https://www.genome.gov/10001345 https://www.genome.gov/10001345
  - jules 11y ago
    It depends on what kind of science it is. Mice are very very similar to humans at a chemical level. They have a similar genome, their bodies are basically the same as ours, they have the same organs, the same blood, the same cells, and the same chemical processes happen in those cells. They are just a bit smaller and arranged in a different way. That explains why scientists use mice as models for humans at all. However, with diseases that happen mostly in the elderly like Alzheimer's and cancer it's not so clear. Mice die at a young age, before those diseases really happen. Mice have to be genetically manipulated to develop those diseases. The development of those artificially caused diseases may not be the same as the development of those diseases in humans. The mice also still have a young body despite having the disease. This makes healing them a lot easier.
  - pbnjay 11y ago
    Mice are ~30% similar genetically to humans, so a surprising amount of transfers. Rats are a bit more similar IIRC, but mice breed quicker so it's easier to do bigger studies... Source: Used to work in mouse research on addiction (alcohol, cocaine, nicotine, etc). Edit: This link gives even more specifics on the similarity: https://www.genome.gov/10001345 https://www.genome.gov/10001345 -- 30% is probably accurate, but in terms of function, it's even higher.
    - sliverstorm 11y ago
      30% similar? Didn't we find that bananas share 50% of genes with humans?
      - plg 11y ago
        that would explain a lot
  - jerf 11y ago
    If it were that low, we would not use them as models. Also bear in mind that mouse models are merely part of a large set of animal models that we use: https://en.wikipedia.org/wiki/List_of_model_organisms#Vertebrates https://en.wikipedia.org/wiki/List_of_model_organisms#Verteb...
- melling 11y ago
  We can also make older mice young again: http://www.businessinsider.com/scientists-make-old-mice-young-again-2013-12 http://www.businessinsider.com/scientists-make-old-mice-youn... The real problem with medicine is that there's no easy way to have "agile" and rapid iteration in humans. Drugs, for example, take decades and billions to get to market.
- refurb 11y ago
  You have a good point. Keep in mind that this is a mouse model of Alzheimer's disease. That is, these mice have a genetic defect that causes similar changes to that seen in human Alzheimer's disease. These mice do not have the same disease as in humans.
- peeters 11y ago
  Relevant West Wing dialog: MARGARET Let me ask you this...Red meat has been found to cause cancer in white rats. Maraschino cherries have been found to cause cancer in white rats. Cellular phones have been found to cause cancer in white rats. Has anyone examined the possibility that cancer might be hereditary in white rats? DR. GRIFFITH Let me tell you something, I'm not 100% sure we've ruled that out.
  - tormeh 11y ago
    Reminds me of a lecturer I had in a neuroscience class that informed us that "no one really checked whether all neurons had the same constants as the ones from the giant squid, but just assumed they did" (or something similar). Apparently anyone who thought of it assumed that something so blindingly obvious would already have been examined by someone else. It took decades before the error was found.
andy_ppp 11y ago
Wow, you can buy some EPPS (the chemical in the article) here for £39.20? http://www.sigmaaldrich.com/catalog/product/sigma/54465?lang=en&region=GB http://www.sigmaaldrich.com/catalog/product/sigma/54465?lang... Looks interesting research but I'm sure this stuff probably can't be that good for you!
- toabi 11y ago
  Shows 137.50€ here :D
  - slight 11y ago
    143.50€ here... (Spain).
    - codecamper 11y ago
      158 euro here. (Morocco) maybe a pricing algorithm that increases price based on demand?
      - PythonicAlpha 11y ago
        Or based on the existence of positive research papers ;)
  - deviarte 11y ago
    $175 here (Netherlands Antilles, Bonaire)
  - twsted 11y ago
    Same (137.50€) from Italy
  - odabaxok 11y ago
    4,265.99 CZK ~ 157.82 EUR (Czech Republic)
  - deleted 11y ago
    [deleted]
eveningcoffee 11y ago
The title is "EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-β oligomers and plaques" and it does not say that it reduces memory, it says "EPPS reduces Aβ-aggregate-induced memory deficits in mice" but they also say that "We observed substantial rescue of working memory deficits in Aβ-infused mice by EPPS treatment". Of course this is only small part of the paper and I have no training to appreciate it more.
- Brakenshire 11y ago
  I'm not an expert either, but as far I can see: The diagramme showing how much memory is recovered is figure one. White is before the administration of the "Alzheimer's protein" (AB protein), black is without the new clearing chemical, blue is with it, and then the different blue columns showing different concentrations. Fig 1c is prophylactic treatment (clearing molecule administered before, during and after the AB protein), Fig 1d is clearing molecule administered alongside AB protein. The impairment seems to more or less recover fully back up to where it was originally, in all four combinations of timing and clearing molecule concentration. But bear in mind: * The mouse model for Alzheimer's seems to be very, very simplified - as far as I can see they literally inject big doses of these proteins directly into the brain in order to induce Alzheimer's like symptoms, that doesn't mean this is equivalent at all to the complex chemical processes underlying Alzheimer's. AB proteins are observed in Alzheimer's patients, but they are also observed in healthy patients, and other proteins are also seen in Alzheimer's patients, some of which are recently thought more likely to be the underlying driver of the disease. * All of this occurs over a very short period of time. Someone who has developed symptoms of Alzheimer's will have had the disease process occurring for many years beforehand. Recovery a few days after administration of the protein doesn't mean that damage would be recoverable years later. Edit: I'm actually just looking at the first experiment, they also do longer term trials with a mouse model which has been genetically altered to over-expresses the AB protein. Arguably this is still a very over-simplified model, but it does more to address the time question. They say Alzheimer's symptoms usually develop at 5 months, then they administer the clearing molecule at 10.5 months for 3 months. Those experiments shows about half the deficit being recovered relative to normal age-matched mice.
- 11y ago
nashashmi 11y ago
I am having an epiphany. Maybe this "Alzheimer protein" is supposed to be the brain's defenses to something much worse. Maybe this protein is a "reaction" similar to skin rashes when it absorbs poison ivy's urisol. If Alzheimer was simply a deficiency of nutrients, I wouldn't think this way, but if it really is a protein that "can be cleared", why did it get there in the first place?
- tdees40 11y ago
  There's a growing body of evidence that Alzheimer's is really just "Type 3 Diabetes": http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/
- jupp0r 11y ago
  I'm not an expert, but human lifespans have only risen to relevant heights very recently. It's simply not enough time for it for evolution to kick in.
  - jonnathanson 11y ago
    Average life expectancy is a commonly misunderstood (and widely misrepresented) concept. We hear things like "Humans really only lived into their 40s in the Stone Age," or what have you. This is untrue. Average (arithmetic mean) life expectancy was a lot lower because it was heavily skewed by infant mortality. Up until very recently, many more babies died within their first few years of life. We've dramatically improved our ability to produce and distribute food and medicine, which has had a profound effect on infant survivability. But we haven't actually lengthened the average life expectancy of an adult who survives the first few years of childhood by all that much. Point is, plenty of people have been living into their 70s, 80s, and 90s for as long as we've existed as a species. That said, the prevalance of diseases like Alzheimer's might be a fairly modern aberration, perhaps owing to lifestyle, environmental, and dietary factors.
    - phil248 11y ago
      Many more people are living in to their 70's, 80's and 90's than previously in human history. While our lifespan may not have increased much, the proportion of people reaching the extreme ends of our lifespan continues to rise. It's not just about infant mortality (not to mention death from childbirth).
reasonattlm 11y ago
If you go digging around you'll find dozens of other similar results in the past five to ten years for dozens of various compounds, some of which produce larger effect sizes than this one. This is nothing to get excited over. It is interesting the way in which various groups leap upon some research reports but not others. The challenge is always having the context for the broader state of research to understand whether it is meaningful or new or not. The present mainstream view of Alzheimer's is that amyloid (and tau) clearance is the way to go. Immunotherapies are the most developed tool, but that is so far proving to be hard - it is too early to say whether failures in clinical trials are because it is hard or because amyloid clearance isn't as useful as thought in this condition. Which could be for any number of reasons including that amyloid-related biochemistry is the problem, but clearing a particular variant or stage of its aggregation doesn't touch that problem area. Amyloid levels in the brain are in fact highly dynamic on a very short timescale. That Alzheimer's develops slowly supports the view that the condition is a slow degeneration of natural clearance mechanisms, such as the filtration performed by the choroid plexus, or the more recently investigated peristaltic passage of fluid out of the brain by other channels. E.g.: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245362/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245362/ On that latter point, the Methuselah Foundation just a few days ago seed funded a startup company that will investigate whether reversing the degeneration of peristaltic fluid passage with aging will improve clearance and thus stop the progression of Alzheimer's. It's based on as yet unpublished work by Doug Ethell at GCBS Western who presented at Rejuvenation Biotechnology 2015 ( http://www.sens.org/files/conferences/rb2015/RB2015-Program.pdf http://www.sens.org/files/conferences/rb2015/RB2015-Program.... ), and has the merit that it should be a fast failure if the theory is wrong, unlike many of the other efforts in Alzheimer's research.
- zepn 11y ago
  Just because I agree with most of your points and there seem to be some overexcited responses to the OP, here are two papers for anyone interested, summarising Aβ and tau [0] and some failures of Aβ therapies [1]. [0] http://www.nature.com/nrn/journal/v12/n2/abs/nrn2967.html http://www.nature.com/nrn/journal/v12/n2/abs/nrn2967.html [1] http://www.nature.com/nrneurol/journal/v9/n12/full/nrneurol.2013.223.html http://www.nature.com/nrneurol/journal/v9/n12/full/nrneurol....
heimatau 11y ago
Ginkgo Biloba [1] is very solid at helping preventing Alzheimer's, even in some cases slowing it down when it's already occurring. Lots of research on the benefits of Ginkgo. Yet most don't know about it. [1] https://duckduckgo.com/?q=ginkgo+biloba+alzheimer+site%3A.edu+OR+site%3A.gov https://duckduckgo.com/?q=ginkgo+biloba+alzheimer+site%3A.ed...
- lg 11y ago
  https://nccih.nih.gov/research/results/gems https://nccih.nih.gov/research/results/gems
  - pbnjay 11y ago
    Quotes to save the clicks... > The dietary supplement Ginkgo biloba was found to be ineffective in reducing the development of dementia and Alzheimer’s disease in older people > The GEM study—the largest of its kind to date—was a randomized, double-blind, placebo-controlled clinical trial of 3,069 community-dwelling adults aged 72 to 96, > Compared with placebo, ginkgo did not lessen cognitive decline. Researchers found no evidence of an effect on cognitive decline in general, or on memory, attention, visual-spatial construction, language, or executive functions. There were no differences by age, sex, race, education, or baseline cognitive status.
- deleted 11y ago
  [deleted]
- blisterpeanuts 11y ago
  Major studies of ginkgo show minimal, if any, benefits.[1] It has not been proven that there are "very solid" benefits of this substance, thus far. http://www.mayoclinic.org/diseases-conditions/alzheimers-disease/expert-answers/ginkgo-biloba-memory-loss/faq-20058119 http://www.mayoclinic.org/diseases-conditions/alzheimers-dis...
- heimatau 11y ago
  Well, I guess everyone loves ideas that re-enforce their own personal beliefs, instead of looking [1] up [2] the various [3] studies that prove this, all you had to do was click through five links and you'd have enough information to dismantle these very common, but unscientific, perspectives. No worries. I'll do the work for you guys since many are just lazy. Here are a handful [4, 5] of sources. It's pretty clear that Gingko DOES work. Low doses (120mg), don't. But that's why I linked to the plethora of research to look into the matter. Finally, source four just makes me laugh because it's clear as day from UMM, that Gingko does work. Also, there are many many more sources that speak to the benefits of Gingko for cognitive repair and slowing down decay. Please don't limit this discussion to the five I listed, hence why I originally linked to search results. Sources (with brief snippets of importance): [1] http://www.ncbi.nlm.nih.gov/pubmed/26268332 http://www.ncbi.nlm.nih.gov/pubmed/26268332 "Ginkgo biloba is potentially beneficial for the improvement of cognitive function, activities of daily living, and global clinical assessment in patients with mild cognitive impairment or Alzheimer's disease." [2] http://www.ncbi.nlm.nih.gov/pubmed/12244890 http://www.ncbi.nlm.nih.gov/pubmed/12244890 "Metaanalysis in the indication--demential disorders--comparing Ginkgo biloba versus acetylcholinesterase inhibitors have shown a similar clinical efficacy of both therapy regimens with an additional drug safety benefit for Ginkgo. Due to the clinical efficacy the WHO accepted Ginkgo biloba as an antidementiv drug and add it in January 2000 into the recent ATC-Classification Index." [3] http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072541/ http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072541/ "The studies showed that people who took the higher dose of the ginkgo extract (240 mg per day) were better able to perform daily activities again, like doing household chores or washing themselves." [4] http://umm.edu/health/medical/altmed/herb/ginkgo-biloba http://umm.edu/health/medical/altmed/herb/ginkgo-biloba "Ginkgo is widely used in Europe for treating dementia. At first, doctors thought it helped because it improves blood flow to the brain. Now research suggests it may protect nerve cells that are damaged in Alzheimer disease. Several studies show that ginkgo has a positive effect on memory and thinking in people with Alzheimer disease or vascular dementia." [5] http://www.ncbi.nlm.nih.gov/pubmed/12519586 http://www.ncbi.nlm.nih.gov/pubmed/12519586 "Overall there is promising evidence of improvement in cognition and function associated with Ginkgo. "
blisterpeanuts 11y ago
This is heartening news; if not a cure, at least it suggests a promising avenue for future research into this terrible condition. This LiveScience[1] article is an easily read summary that also mentions a critique of the approach. Given the unfortunate history[2][3] of falsified Korean scientific research, it would be prudent to withhold judgment until these results have been reproduced in other labs around the world. 1. http://www.livescience.com/53019-epps-chemical-washes-away-alzheimers-plaque.html http://www.livescience.com/53019-epps-chemical-washes-away-a... 2. http://www.nytimes.com/2009/10/27/world/asia/27clone.html?_r=0 http://www.nytimes.com/2009/10/27/world/asia/27clone.html?_r... 3. https://www.washingtonpost.com/news/to-your-health/wp/2015/07/01/researcher-who-spiked-rabbit-blood-to-fake-hiv-vaccine-results-slapped-with-rare-prison-sentence/ https://www.washingtonpost.com/news/to-your-health/wp/2015/0...
- decisiveness 11y ago
  This seems like a pretty unfair generalization of Koreans. Assuming all scientists have the same shameful characteristics of a few doesn't seem very scientific, does it?
  - irishloop 11y ago
    I think it's more of a generalization of the Korean scientific community, of which most Koreans are not a part.
    - celticninja 11y ago
      It is an unfair generalisation in both cases. The wiki list of scientific fraud examples is very heavy on US examples.
      - blisterpeanuts 11y ago
        What's the ratio of U.S. scientists to Korean scientists? 10:1 or so? I would expect to see 10x as many fraud cases in the U.S. But there have been some doozies in Korean science, especially the stem cell guy who really embarrassed and shamed his country with the extent of deception he practiced. Brilliant, but also crazy.
midnitewarrior 11y ago
Wow, they've prevented Alzheimer's in healthy mice, and restored memory function to sick Alzheimer's affected mice. The treatment is non-toxic at ridiculous levels too.
antidaily 11y ago
BUT it makes for pet chimpanzee super smart and and ruins human civilization, setting up en epic battle between apes and men.
aantix 11y ago
A slightly unrelated question; are there any companies out there that are working on a replacement for mouse models in disease research? I'm think more in terms of computer simulation?
- bosdev 11y ago
  Yes, but it's incredibly complicated.
daveguy 11y ago
I would like to point out that the main study described in this article is not the "inject aggregated amyloid beta fibrils" that is described first. That study was a preliminary study that prompted the main study which uses genetically altered mice. The test for alzheimers for the first study (previously reported but summarized again) was to quantify how much the mice deviates from solving a maze that they have been trained to solve. In the first they injected amyloid beta aggregates into mouse brains and found that EPPS administered orally at 30 mg/kg and 100 mg/kg restores the ability of the mice to efficiently solve the maze. Next they tested toxicity quantified the amount of EPPS that passes the brain/blood barrier. For toxicity they found no signs of toxicity at 2000 mg / kg (20x dosage). For blood/brain barrier, as you go up in blood concentration you should go up in brain concentration if there is a good penetration from blood to brain. If the barrier is high then you immediately get high blood and low brain concentrations. The point where there is no longer a significant increase in brain concentration when increasing blood concentration is used to determine effective dosage concentrations. They found that at 100 mg/kg they were starting to see increased blood/brain ratios so they targeted 10-100 mg/kg for the next study. MAIN STUDY (which included identifying the dosage level) used mice that were engineered to "get Alzheimer's" starting around 5 months of age because they produce a human gene (transgenic) that is a precursor to form the AB plaques. This transgenic model is established and the mice showed the expected amyloid beta plaques and had difficulty solving the maze at 10.5 months as expected. Starting at 10.5 months they gave oral doses of EPPS at 10 mg/kg and 30 mg/kg and monitored maze solving along with several additional tests: likelihood to freeze when presented with negative input (fear conditioning) and ability to find hidden platforms when swimming (water maze). Both tests improved significantly to the wild-type (no Alzheimer's) level when taking EPPS. They also did dose dependency at .1 1 and 10 mg/kg. There was a steady improvement at higher doses. They also took slices of the mouse brain and tested whether or not the neurons responded differently to electrical stimulation. They found no difference in wild-type (WT, non-genetically altered) or transgenic (TG, altered) response to electrical stimulation with and without EPPS. This hints at no difference in neural activity with or without EPPS. They also gave EPPS to WT for the behavioral tests and did not see a difference (although that was not shown in the behavioral test figures). They also took slices of the brain and stained them with a fluorescent dye to show the Alzheimer's associated plaques. There is a significant quantifiable reduction in plaques in the treated mice. They used several other techniques to confirm that they were actually AB plaques and they disaggregated by a specific site of activity. I won't go into those specifics, but to say that this was a VERY well designed and executed study across multiple lines of inquiry and all of the lines of inquiry point to the same conclusion: EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-b oligomers and plaques And that's why it's a Nature article.
openbsdway 11y ago
Perhaps Pinky can now stop asking Brain what it is they will be doing tonight!

452 points by coris47 11y ago

keeptrying 11y ago

There have been at least 3 previous solutions for AD in mice which have never panned out in humans.

brwnll 11y ago
Source?
- pcrh 11y ago
  Actually its more like 300 treatments that haven't panned-out... ‘Too much good news’ – are Alzheimer mouse models trying to tell us how to prevent, not cure, Alzheimer’s disease? https://www.ncbi.nlm.nih.gov/pubmed/?term=20542579 https://www.ncbi.nlm.nih.gov/pubmed/?term=20542579

plg 11y ago

it's a great day for mouse health

wiremine 11y ago
You say that tongue in cheek, but as a non-scientist, I've always wondered how much "mouse science" ultimately translates to humans. My guess is it's very low, but knowing a percentage would help me better understand how to proceed reports like this.
- moioci 11y ago
  Not all that low: https://www.genome.gov/10001345 https://www.genome.gov/10001345
- jules 11y ago
  It depends on what kind of science it is. Mice are very very similar to humans at a chemical level. They have a similar genome, their bodies are basically the same as ours, they have the same organs, the same blood, the same cells, and the same chemical processes happen in those cells. They are just a bit smaller and arranged in a different way. That explains why scientists use mice as models for humans at all. However, with diseases that happen mostly in the elderly like Alzheimer's and cancer it's not so clear. Mice die at a young age, before those diseases really happen. Mice have to be genetically manipulated to develop those diseases. The development of those artificially caused diseases may not be the same as the development of those diseases in humans. The mice also still have a young body despite having the disease. This makes healing them a lot easier.
- pbnjay 11y ago
  Mice are ~30% similar genetically to humans, so a surprising amount of transfers. Rats are a bit more similar IIRC, but mice breed quicker so it's easier to do bigger studies... Source: Used to work in mouse research on addiction (alcohol, cocaine, nicotine, etc). Edit: This link gives even more specifics on the similarity: https://www.genome.gov/10001345 https://www.genome.gov/10001345 -- 30% is probably accurate, but in terms of function, it's even higher.
  - sliverstorm 11y ago
    30% similar? Didn't we find that bananas share 50% of genes with humans?
    - plg 11y ago
      that would explain a lot
- jerf 11y ago
  If it were that low, we would not use them as models. Also bear in mind that mouse models are merely part of a large set of animal models that we use: https://en.wikipedia.org/wiki/List_of_model_organisms#Vertebrates https://en.wikipedia.org/wiki/List_of_model_organisms#Verteb...
melling 11y ago
We can also make older mice young again: http://www.businessinsider.com/scientists-make-old-mice-young-again-2013-12 http://www.businessinsider.com/scientists-make-old-mice-youn... The real problem with medicine is that there's no easy way to have "agile" and rapid iteration in humans. Drugs, for example, take decades and billions to get to market.
refurb 11y ago
You have a good point. Keep in mind that this is a mouse model of Alzheimer's disease. That is, these mice have a genetic defect that causes similar changes to that seen in human Alzheimer's disease. These mice do not have the same disease as in humans.
peeters 11y ago
Relevant West Wing dialog: MARGARET Let me ask you this...Red meat has been found to cause cancer in white rats. Maraschino cherries have been found to cause cancer in white rats. Cellular phones have been found to cause cancer in white rats. Has anyone examined the possibility that cancer might be hereditary in white rats? DR. GRIFFITH Let me tell you something, I'm not 100% sure we've ruled that out.
- tormeh 11y ago
  Reminds me of a lecturer I had in a neuroscience class that informed us that "no one really checked whether all neurons had the same constants as the ones from the giant squid, but just assumed they did" (or something similar). Apparently anyone who thought of it assumed that something so blindingly obvious would already have been examined by someone else. It took decades before the error was found.

andy_ppp 11y ago

Wow, you can buy some EPPS (the chemical in the article) here for £39.20? http://www.sigmaaldrich.com/catalog/product/sigma/54465?lang=en&region=GB http://www.sigmaaldrich.com/catalog/product/sigma/54465?lang... Looks interesting research but I'm sure this stuff probably can't be that good for you!

toabi 11y ago
Shows 137.50€ here :D
- slight 11y ago
  143.50€ here... (Spain).
  - codecamper 11y ago
    158 euro here. (Morocco) maybe a pricing algorithm that increases price based on demand?
    - PythonicAlpha 11y ago
      Or based on the existence of positive research papers ;)
- deviarte 11y ago
  $175 here (Netherlands Antilles, Bonaire)
- twsted 11y ago
  Same (137.50€) from Italy
- odabaxok 11y ago
  4,265.99 CZK ~ 157.82 EUR (Czech Republic)
- deleted 11y ago
  [deleted]

eveningcoffee 11y ago

The title is "EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-β oligomers and plaques" and it does not say that it reduces memory, it says "EPPS reduces Aβ-aggregate-induced memory deficits in mice" but they also say that "We observed substantial rescue of working memory deficits in Aβ-infused mice by EPPS treatment". Of course this is only small part of the paper and I have no training to appreciate it more.

Brakenshire 11y ago
I'm not an expert either, but as far I can see: The diagramme showing how much memory is recovered is figure one. White is before the administration of the "Alzheimer's protein" (AB protein), black is without the new clearing chemical, blue is with it, and then the different blue columns showing different concentrations. Fig 1c is prophylactic treatment (clearing molecule administered before, during and after the AB protein), Fig 1d is clearing molecule administered alongside AB protein. The impairment seems to more or less recover fully back up to where it was originally, in all four combinations of timing and clearing molecule concentration. But bear in mind: * The mouse model for Alzheimer's seems to be very, very simplified - as far as I can see they literally inject big doses of these proteins directly into the brain in order to induce Alzheimer's like symptoms, that doesn't mean this is equivalent at all to the complex chemical processes underlying Alzheimer's. AB proteins are observed in Alzheimer's patients, but they are also observed in healthy patients, and other proteins are also seen in Alzheimer's patients, some of which are recently thought more likely to be the underlying driver of the disease. * All of this occurs over a very short period of time. Someone who has developed symptoms of Alzheimer's will have had the disease process occurring for many years beforehand. Recovery a few days after administration of the protein doesn't mean that damage would be recoverable years later. Edit: I'm actually just looking at the first experiment, they also do longer term trials with a mouse model which has been genetically altered to over-expresses the AB protein. Arguably this is still a very over-simplified model, but it does more to address the time question. They say Alzheimer's symptoms usually develop at 5 months, then they administer the clearing molecule at 10.5 months for 3 months. Those experiments shows about half the deficit being recovered relative to normal age-matched mice.
11y ago

nashashmi 11y ago

I am having an epiphany. Maybe this "Alzheimer protein" is supposed to be the brain's defenses to something much worse. Maybe this protein is a "reaction" similar to skin rashes when it absorbs poison ivy's urisol. If Alzheimer was simply a deficiency of nutrients, I wouldn't think this way, but if it really is a protein that "can be cleared", why did it get there in the first place?

tdees40 11y ago
There's a growing body of evidence that Alzheimer's is really just "Type 3 Diabetes": http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/
jupp0r 11y ago
I'm not an expert, but human lifespans have only risen to relevant heights very recently. It's simply not enough time for it for evolution to kick in.
- jonnathanson 11y ago
  Average life expectancy is a commonly misunderstood (and widely misrepresented) concept. We hear things like "Humans really only lived into their 40s in the Stone Age," or what have you. This is untrue. Average (arithmetic mean) life expectancy was a lot lower because it was heavily skewed by infant mortality. Up until very recently, many more babies died within their first few years of life. We've dramatically improved our ability to produce and distribute food and medicine, which has had a profound effect on infant survivability. But we haven't actually lengthened the average life expectancy of an adult who survives the first few years of childhood by all that much. Point is, plenty of people have been living into their 70s, 80s, and 90s for as long as we've existed as a species. That said, the prevalance of diseases like Alzheimer's might be a fairly modern aberration, perhaps owing to lifestyle, environmental, and dietary factors.
  - phil248 11y ago
    Many more people are living in to their 70's, 80's and 90's than previously in human history. While our lifespan may not have increased much, the proportion of people reaching the extreme ends of our lifespan continues to rise. It's not just about infant mortality (not to mention death from childbirth).

reasonattlm 11y ago

If you go digging around you'll find dozens of other similar results in the past five to ten years for dozens of various compounds, some of which produce larger effect sizes than this one. This is nothing to get excited over. It is interesting the way in which various groups leap upon some research reports but not others. The challenge is always having the context for the broader state of research to understand whether it is meaningful or new or not. The present mainstream view of Alzheimer's is that amyloid (and tau) clearance is the way to go. Immunotherapies are the most developed tool, but that is so far proving to be hard - it is too early to say whether failures in clinical trials are because it is hard or because amyloid clearance isn't as useful as thought in this condition. Which could be for any number of reasons including that amyloid-related biochemistry is the problem, but clearing a particular variant or stage of its aggregation doesn't touch that problem area. Amyloid levels in the brain are in fact highly dynamic on a very short timescale. That Alzheimer's develops slowly supports the view that the condition is a slow degeneration of natural clearance mechanisms, such as the filtration performed by the choroid plexus, or the more recently investigated peristaltic passage of fluid out of the brain by other channels. E.g.: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245362/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245362/ On that latter point, the Methuselah Foundation just a few days ago seed funded a startup company that will investigate whether reversing the degeneration of peristaltic fluid passage with aging will improve clearance and thus stop the progression of Alzheimer's. It's based on as yet unpublished work by Doug Ethell at GCBS Western who presented at Rejuvenation Biotechnology 2015 ( http://www.sens.org/files/conferences/rb2015/RB2015-Program.pdf http://www.sens.org/files/conferences/rb2015/RB2015-Program.... ), and has the merit that it should be a fast failure if the theory is wrong, unlike many of the other efforts in Alzheimer's research.

zepn 11y ago
Just because I agree with most of your points and there seem to be some overexcited responses to the OP, here are two papers for anyone interested, summarising Aβ and tau [0] and some failures of Aβ therapies [1]. [0] http://www.nature.com/nrn/journal/v12/n2/abs/nrn2967.html http://www.nature.com/nrn/journal/v12/n2/abs/nrn2967.html [1] http://www.nature.com/nrneurol/journal/v9/n12/full/nrneurol.2013.223.html http://www.nature.com/nrneurol/journal/v9/n12/full/nrneurol....

heimatau 11y ago

Ginkgo Biloba [1] is very solid at helping preventing Alzheimer's, even in some cases slowing it down when it's already occurring. Lots of research on the benefits of Ginkgo. Yet most don't know about it. [1] https://duckduckgo.com/?q=ginkgo+biloba+alzheimer+site%3A.edu+OR+site%3A.gov https://duckduckgo.com/?q=ginkgo+biloba+alzheimer+site%3A.ed...

lg 11y ago
https://nccih.nih.gov/research/results/gems https://nccih.nih.gov/research/results/gems
- pbnjay 11y ago
  Quotes to save the clicks... > The dietary supplement Ginkgo biloba was found to be ineffective in reducing the development of dementia and Alzheimer’s disease in older people > The GEM study—the largest of its kind to date—was a randomized, double-blind, placebo-controlled clinical trial of 3,069 community-dwelling adults aged 72 to 96, > Compared with placebo, ginkgo did not lessen cognitive decline. Researchers found no evidence of an effect on cognitive decline in general, or on memory, attention, visual-spatial construction, language, or executive functions. There were no differences by age, sex, race, education, or baseline cognitive status.
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blisterpeanuts 11y ago
Major studies of ginkgo show minimal, if any, benefits.[1] It has not been proven that there are "very solid" benefits of this substance, thus far. http://www.mayoclinic.org/diseases-conditions/alzheimers-disease/expert-answers/ginkgo-biloba-memory-loss/faq-20058119 http://www.mayoclinic.org/diseases-conditions/alzheimers-dis...
heimatau 11y ago
Well, I guess everyone loves ideas that re-enforce their own personal beliefs, instead of looking [1] up [2] the various [3] studies that prove this, all you had to do was click through five links and you'd have enough information to dismantle these very common, but unscientific, perspectives. No worries. I'll do the work for you guys since many are just lazy. Here are a handful [4, 5] of sources. It's pretty clear that Gingko DOES work. Low doses (120mg), don't. But that's why I linked to the plethora of research to look into the matter. Finally, source four just makes me laugh because it's clear as day from UMM, that Gingko does work. Also, there are many many more sources that speak to the benefits of Gingko for cognitive repair and slowing down decay. Please don't limit this discussion to the five I listed, hence why I originally linked to search results. Sources (with brief snippets of importance): [1] http://www.ncbi.nlm.nih.gov/pubmed/26268332 http://www.ncbi.nlm.nih.gov/pubmed/26268332 "Ginkgo biloba is potentially beneficial for the improvement of cognitive function, activities of daily living, and global clinical assessment in patients with mild cognitive impairment or Alzheimer's disease." [2] http://www.ncbi.nlm.nih.gov/pubmed/12244890 http://www.ncbi.nlm.nih.gov/pubmed/12244890 "Metaanalysis in the indication--demential disorders--comparing Ginkgo biloba versus acetylcholinesterase inhibitors have shown a similar clinical efficacy of both therapy regimens with an additional drug safety benefit for Ginkgo. Due to the clinical efficacy the WHO accepted Ginkgo biloba as an antidementiv drug and add it in January 2000 into the recent ATC-Classification Index." [3] http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072541/ http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072541/ "The studies showed that people who took the higher dose of the ginkgo extract (240 mg per day) were better able to perform daily activities again, like doing household chores or washing themselves." [4] http://umm.edu/health/medical/altmed/herb/ginkgo-biloba http://umm.edu/health/medical/altmed/herb/ginkgo-biloba "Ginkgo is widely used in Europe for treating dementia. At first, doctors thought it helped because it improves blood flow to the brain. Now research suggests it may protect nerve cells that are damaged in Alzheimer disease. Several studies show that ginkgo has a positive effect on memory and thinking in people with Alzheimer disease or vascular dementia." [5] http://www.ncbi.nlm.nih.gov/pubmed/12519586 http://www.ncbi.nlm.nih.gov/pubmed/12519586 "Overall there is promising evidence of improvement in cognition and function associated with Ginkgo. "

blisterpeanuts 11y ago

This is heartening news; if not a cure, at least it suggests a promising avenue for future research into this terrible condition. This LiveScience[1] article is an easily read summary that also mentions a critique of the approach. Given the unfortunate history[2][3] of falsified Korean scientific research, it would be prudent to withhold judgment until these results have been reproduced in other labs around the world. 1. http://www.livescience.com/53019-epps-chemical-washes-away-alzheimers-plaque.html http://www.livescience.com/53019-epps-chemical-washes-away-a... 2. http://www.nytimes.com/2009/10/27/world/asia/27clone.html?_r=0 http://www.nytimes.com/2009/10/27/world/asia/27clone.html?_r... 3. https://www.washingtonpost.com/news/to-your-health/wp/2015/07/01/researcher-who-spiked-rabbit-blood-to-fake-hiv-vaccine-results-slapped-with-rare-prison-sentence/ https://www.washingtonpost.com/news/to-your-health/wp/2015/0...

decisiveness 11y ago
This seems like a pretty unfair generalization of Koreans. Assuming all scientists have the same shameful characteristics of a few doesn't seem very scientific, does it?
- irishloop 11y ago
  I think it's more of a generalization of the Korean scientific community, of which most Koreans are not a part.
  - celticninja 11y ago
    It is an unfair generalisation in both cases. The wiki list of scientific fraud examples is very heavy on US examples.
    - blisterpeanuts 11y ago
      What's the ratio of U.S. scientists to Korean scientists? 10:1 or so? I would expect to see 10x as many fraud cases in the U.S. But there have been some doozies in Korean science, especially the stem cell guy who really embarrassed and shamed his country with the extent of deception he practiced. Brilliant, but also crazy.

midnitewarrior 11y ago

Wow, they've prevented Alzheimer's in healthy mice, and restored memory function to sick Alzheimer's affected mice. The treatment is non-toxic at ridiculous levels too.

antidaily 11y ago

BUT it makes for pet chimpanzee super smart and and ruins human civilization, setting up en epic battle between apes and men.

aantix 11y ago

A slightly unrelated question; are there any companies out there that are working on a replacement for mouse models in disease research? I'm think more in terms of computer simulation?

bosdev 11y ago
Yes, but it's incredibly complicated.

daveguy 11y ago

I would like to point out that the main study described in this article is not the "inject aggregated amyloid beta fibrils" that is described first. That study was a preliminary study that prompted the main study which uses genetically altered mice. The test for alzheimers for the first study (previously reported but summarized again) was to quantify how much the mice deviates from solving a maze that they have been trained to solve. In the first they injected amyloid beta aggregates into mouse brains and found that EPPS administered orally at 30 mg/kg and 100 mg/kg restores the ability of the mice to efficiently solve the maze. Next they tested toxicity quantified the amount of EPPS that passes the brain/blood barrier. For toxicity they found no signs of toxicity at 2000 mg / kg (20x dosage). For blood/brain barrier, as you go up in blood concentration you should go up in brain concentration if there is a good penetration from blood to brain. If the barrier is high then you immediately get high blood and low brain concentrations. The point where there is no longer a significant increase in brain concentration when increasing blood concentration is used to determine effective dosage concentrations. They found that at 100 mg/kg they were starting to see increased blood/brain ratios so they targeted 10-100 mg/kg for the next study. MAIN STUDY (which included identifying the dosage level) used mice that were engineered to "get Alzheimer's" starting around 5 months of age because they produce a human gene (transgenic) that is a precursor to form the AB plaques. This transgenic model is established and the mice showed the expected amyloid beta plaques and had difficulty solving the maze at 10.5 months as expected. Starting at 10.5 months they gave oral doses of EPPS at 10 mg/kg and 30 mg/kg and monitored maze solving along with several additional tests: likelihood to freeze when presented with negative input (fear conditioning) and ability to find hidden platforms when swimming (water maze). Both tests improved significantly to the wild-type (no Alzheimer's) level when taking EPPS. They also did dose dependency at .1 1 and 10 mg/kg. There was a steady improvement at higher doses. They also took slices of the mouse brain and tested whether or not the neurons responded differently to electrical stimulation. They found no difference in wild-type (WT, non-genetically altered) or transgenic (TG, altered) response to electrical stimulation with and without EPPS. This hints at no difference in neural activity with or without EPPS. They also gave EPPS to WT for the behavioral tests and did not see a difference (although that was not shown in the behavioral test figures). They also took slices of the brain and stained them with a fluorescent dye to show the Alzheimer's associated plaques. There is a significant quantifiable reduction in plaques in the treated mice. They used several other techniques to confirm that they were actually AB plaques and they disaggregated by a specific site of activity. I won't go into those specifics, but to say that this was a VERY well designed and executed study across multiple lines of inquiry and all of the lines of inquiry point to the same conclusion: EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-b oligomers and plaques And that's why it's a Nature article.

openbsdway 11y ago

Perhaps Pinky can now stop asking Brain what it is they will be doing tonight!