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-a...

2. http://www.nytimes.com/2009/10/27/world/asia/27clone.html?_r...

3. https://www.washingtonpost.com/news/to-your-health/wp/2015/0...

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!

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/

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fluid passage with aging will improve clearance and thus stop the progression of Alzheimer's. It's based on as yet unpublished work by Doug Ethell at GCBS Western who presented at Rejuvenation Biotechnology 2015 ( http://www.sens.org/files/conferences/rb2015/RB2015-Program.... ), 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.

Of course this is only small part of the paper and I have no training to appreciate it more.

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?

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.

I'm think more in terms of computer simulation?

[1] https://duckduckgo.com/?q=ginkgo+biloba+alzheimer+site%3A.ed...

I'd take any health risks over dementia, personally, and I'm sure most would, too. Looking forward to the FDA blocking this on "safety" grounds.

(http://www.ncbi.nlm.nih.gov/pubmed/19558257)

It kind of scares me that people think they can buy untested chemicals online and self-medicate with them. But then again I'm not into the whole "Bath Salts" scene which is all about that.

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.

It's one of the major deficits in ADHD, to the extent that clarifies what the effects might be.

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.

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.

Your core question is a good one and fundamentally raises the question of causality (which came first, the A-beta or Alzheimer's disease, AD? See ref. 1 for a 'simple' discussion).

Interesting evidence comes from people with genetic mutations that decrease the levels of the precursor to A-beta (the protein associated with Alzheimer's plaques). People with these mutations are less likely to develop AD, suggesting that A-beta is related to the root cause of AD. The OP supports this evidence, as removing A-beta plaques ameliorates some memory loss.

As a final, unrelated note, I don't know much dermatology but I haven't gotten the sense that our response to uroshiol is considered protective. Unlike A-beta, uroshiol is directly causative of its associated clinical symptoms[3].

1. http://www.mayoclinic.org/diseases-conditions/alzheimers-dis... 2. http://www.ncbi.nlm.nih.gov/pubmed/22801501 3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC294319/

What could possibly be worse? What are we seeing from non-Alzheimer sufferers that's so terrible? I don't think there's any evidence here that there's some benefit to it. Its a horrible disease.

My dad went from occasional forgetfulness to completely falling apart in less than two years. He would get lost routinely, couldn't remember names, had no idea what time or day it was, and developed sundown syndrome where once 6pm hit he completely went mad. He would be angry at nothing and scream at the mirror. He would rant and ramble about his past or strange conspiracy theories. Towards the end, he lived in some weird nightmarish state almost all the time. Sundown syndrome became his norm. He died of cancer before it progressed past that point, but man, this disease is not just losing memories. It pretty much destroys your brain and acute dementia has a link with immune system dysfunction, so it eventually kills you, usually by pneumonia.

I doubt there's any benefit. Evolution isn't this wonderful process. Its a lot of crap thrown at the wall and enjoying the stuff that works and dealing with what doesn't. There's no mastermind or clockmaker here. There are a lot of things that go wrong with human health that has no benefit.

Since dementia is a disease that happens at a late age, there doesn't need to be a reason why it is there. It happens a long time after reproduction, so its effect on evolution is minimal, worse it could even be evolved as a mechanism to curb older specimens in the species.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/

http://www.mayoclinic.org/diseases-conditions/alzheimers-dis...

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 "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 "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/ "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 "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 "Overall there is promising evidence of improvement in cognition and function associated with Ginkgo. "