Alzheimers Research Questioned

marting · 23rd July 2022, 04:45 PM

A neuroscience image sleuth finds signs of fabrication in scores of Alzheimer’s articles, threatening a reigning theory of the disease

https://www.science.org/content/arti...eimers-disease

Quote:

A 6-month investigation by Science provided strong support for Schrag’s suspicions and raised questions about Lesné’s research. A leading independent image analyst and several top Alzheimer’s researchers—including George Perry of the University of Texas, San Antonio, and John Forsayeth of the University of California, San Francisco (UCSF)—reviewed most of Schrag’s findings at Science’s request. They concurred with his overall conclusions, which cast doubt on hundreds of images, including more than 70 in Lesné’s papers. Some look like “shockingly blatant” examples of image tampering, says Donna Wilcock, an Alzheimer’s expert at the University of Kentucky.

Just wow.

whoanellie · 23rd July 2022, 05:18 PM

Fascinating . Thanks for posting this.

Gord_in_Toronto · 23rd July 2022, 06:00 PM

It will be interesting to see how this plays out. If results have been faked as the whistle blower suggests, this is a fraud of immense magnitude and has caused the waste of millions on falsely predicated research.

The first tip off (to me, anyway) that there really may be something wrong is the quote from the article:

Quote:

In the 16 years following the landmark paper, Lesné and Ashe—separately or jointly—published many articles on their stellar oligomer. Yet only a handful of other groups have reported detecting Aβ*56.

Remember the REPLICATION part of experimental science?

Mike! · 24th July 2022, 05:23 AM

Shades of the Bastard Wakefield's "work" in Autism and vaccines?

Hellbound · 25th July 2022, 07:48 AM

Originally Posted by Gord_in_Toronto

Remember the REPLICATION part of experimental science?

Yeah, that’s often forgotten. As I repeatedly tell my son, the reason we look for published scientific articles isn’t because they’re proof, in and of themselves. It’s because that’s really the start of the scientific investigation, so to speak. A paper should give all the info necessary for replication, and replication is really what determines if it’s a theory that should be accepted.

Sent from my volcanic island lair using carrier pigeon.

Darat · 25th July 2022, 07:52 AM

Originally Posted by Hellbound

Yeah, that’s often forgotten. As I repeatedly tell my son, the reason we look for published scientific articles isn’t because they’re proof, in and of themselves. It’s because that’s really the start of the scientific investigation, so to speak. A paper should give all the info necessary for replication, and replication is really what determines if it’s a theory that should be accepted.

Sent from my volcanic island lair using carrier pigeon.

Problem is that it can be very difficult to get a grant for doing the same thing someone else has already done and published so what tends to happen is the "replication" has to come from "adjacent" research or drawn together by a metanalyses.

Gord_in_Toronto · 25th July 2022, 10:03 AM

Originally Posted by Darat

Problem is that it can be very difficult to get a grant for doing the same thing someone else has already done and published so what tends to happen is the "replication" has to come from "adjacent" research or drawn together by a metanalyses.

Yes, I think this is true but it is possible to get a grant to extend the original research and that extension that must de facto replicate the original research and either substantiate it or call it into question.

The problem in so many cases is an INSUFFICIENT SAMPLE SIZE. And the difficulty there is that getting a good sample is usually so expensive.

I used to follow quite closely what was going on at the National Center for Complementary and Integrative Health (US) and at least they were honest enough in their testing of the effectiveness of such as Balboa Ginkgo Juice was that in the vast majority of cases, "more testing was required". Well what did you expect when you tested it on 34 people and only 27 completed the study?

On a personal note. I once was part of a study that extended research that had demonstrated that having protein for breakfast enhanced your muscle strength. It was designed to show that having protein for your evening meal as well worked even better. The study involved providing me with free food for eight weeks, multiple daylong lab visits, supervised weight lifting and running, continuous blood sampling and, painful, muscle biopsies. ISTR there were about thirty participants divided between the real test group (I turned out to in that after the blinding was undone) and the control group. Oh, and they paid me a couple of hundred for my time. I would hazard a guess that the project grant was at least in the tens of thousands. The resulting paper got the study's leader her PhD and advanced the cause of science by an infinitesimal amount.

theprestige · 25th July 2022, 10:47 AM

Originally Posted by Hellbound

Yeah, that’s often forgotten. As I repeatedly tell my son, the reason we look for published scientific articles isn’t because they’re proof, in and of themselves. It’s because that’s really the start of the scientific investigation, so to speak. A paper should give all the info necessary for replication, and replication is really what determines if it’s a theory that should be accepted.

Sent from my volcanic island lair using carrier pigeon.

Originally Posted by Darat

Problem is that it can be very difficult to get a grant for doing the same thing someone else has already done and published so what tends to happen is the "replication" has to come from "adjacent" research or drawn together by a metanalyses.

Which raises all sorts of questions about scientific "truths" we take for granted. On the one hand, you have a perverse incentive to make sure your results are consistent with previous results. And on the other hand, you have a perverse incentive to not try replicating previous results.

casebro · 25th July 2022, 03:22 PM

Maybe the researchers forgot what they came into the lab for.

Tero · 25th July 2022, 07:57 PM

Throwing all that out does not exclude the amyloid plaques as part of the disease.
https://en.wikipedia.org/wiki/Amyloid_plaques

Their formation still needs to be studied, as well as intracellular proteins.

Lithrael · 26th July 2022, 04:32 PM

Yeah, though this is a mess, the "16 years of research wasted because of faked paper" stuff is hyperbole. There's a good basic followup blog post also on Science.

https://www.science.org/content/blog...t-does-it-mean

"Lesné’s work now appears suspect across his entire publication record. AB*56 itself does not seem to exist. Other researchers had failed to find it even in the first years after the 2006 publication, but that did not slow the beta-amyloid-oligomer field down at all. It was going to grow anyway, but it’s for sure that the AB*56 stuff turbocharged it, too. Amyloid oligomers are a huge tangled area with all kinds of stuff to work on, and while no one could really prove that any particular oligomeric species was the cause of Alzheimer’s, no one could prove that there wasn’t such a causative agent, either, of course.

It’s definitely fair to say that the Lesné work caused trials to happen more quickly and probably in greater number than they would have otherwise.

Those trials have failed. But every single Alzheimer’s trial has failed. I think that any ultimate explanation of Alzheimer’s disease is going to have to include beta-amyloid as a big part of the story - but if attacking the disease from that standpoint is going to lead to viable treatments, we sure as hell haven’t been seeing it. We have to put money and effort down on other hypotheses and stop hammering, hammering, hammering on beta-amyloid so much. It isn’t working."

23rd July 2022, 04:45 PM	#1
marting Illuminator Join Date: Sep 2003 Posts: 3,362	Alzheimers Research Questioned A neuroscience image sleuth finds signs of fabrication in scores of Alzheimer’s articles, threatening a reigning theory of the disease https://www.science.org/content/arti...eimers-disease Quote: A 6-month investigation by Science provided strong support for Schrag’s suspicions and raised questions about Lesné’s research. A leading independent image analyst and several top Alzheimer’s researchers—including George Perry of the University of Texas, San Antonio, and John Forsayeth of the University of California, San Francisco (UCSF)—reviewed most of Schrag’s findings at Science’s request. They concurred with his overall conclusions, which cast doubt on hundreds of images, including more than 70 in Lesné’s papers. Some look like “shockingly blatant” examples of image tampering, says Donna Wilcock, an Alzheimer’s expert at the University of Kentucky. Just wow.
marting Illuminator Join Date: Sep 2003 Posts: 3,362	__________________ Flying's easy. Walking on water, now that's cool.

23rd July 2022, 06:00 PM	#3
Gord_in_Toronto Penultimate Amazing Join Date: Jul 2006 Posts: 22,713	It will be interesting to see how this plays out. If results have been faked as the whistle blower suggests, this is a fraud of immense magnitude and has caused the waste of millions on falsely predicated research. The first tip off (to me, anyway) that there really may be something wrong is the quote from the article: Quote: In the 16 years following the landmark paper, Lesné and Ashe—separately or jointly—published many articles on their stellar oligomer. Yet only a handful of other groups have reported detecting Aβ*56. Remember the REPLICATION part of experimental science?
	__________________ "Reality is what's left when you cease to believe." Philip K. Dick

24th July 2022, 05:23 AM	#4
Mike! Official Ponylandistanian National Treasure. Respect it! Join Date: May 2010 Location: Ponylandistan! Where the bacon grows on trees! Can it get any better than that? I submit it can not! Posts: 46,555	Shades of the Bastard Wakefield's "work" in Autism and vaccines?
	__________________ "Never judge a man until you’ve walked a mile in his shoes... Because then it won't really matter, you’ll be a mile away and have his shoes."

25th July 2022, 07:48 AM	#5
Hellbound Merchant of Doom Join Date: Sep 2002 Location: Not in Hell, but I can see it from here on a clear day... Posts: 14,889	Originally Posted by Gord_in_Toronto Remember the REPLICATION part of experimental science? Yeah, that’s often forgotten. As I repeatedly tell my son, the reason we look for published scientific articles isn’t because they’re proof, in and of themselves. It’s because that’s really the start of the scientific investigation, so to speak. A paper should give all the info necessary for replication, and replication is really what determines if it’s a theory that should be accepted. Sent from my volcanic island lair using carrier pigeon.
	__________________ History does not always repeat itself. Sometimes it just yells "Can't you remember anything I told you?" and lets fly with a club. - John w. Campbell

25th July 2022, 07:52 AM	#6
Darat Lackey Administrator Join Date: Aug 2001 Location: South East, UK Posts: 103,196	Originally Posted by Hellbound Yeah, that’s often forgotten. As I repeatedly tell my son, the reason we look for published scientific articles isn’t because they’re proof, in and of themselves. It’s because that’s really the start of the scientific investigation, so to speak. A paper should give all the info necessary for replication, and replication is really what determines if it’s a theory that should be accepted. Sent from my volcanic island lair using carrier pigeon. Problem is that it can be very difficult to get a grant for doing the same thing someone else has already done and published so what tends to happen is the "replication" has to come from "adjacent" research or drawn together by a metanalyses.
	__________________ I wish I knew how to quit you

23rd July 2022, 05:18 PM	#2
whoanellie Graduate Poster Join Date: Apr 2012 Posts: 1,101	Fascinating . Thanks for posting this.

25th July 2022, 10:03 AM	#7
Gord_in_Toronto Penultimate Amazing Join Date: Jul 2006 Posts: 22,713	Originally Posted by Darat Problem is that it can be very difficult to get a grant for doing the same thing someone else has already done and published so what tends to happen is the "replication" has to come from "adjacent" research or drawn together by a metanalyses. Yes, I think this is true but it is possible to get a grant to extend the original research and that extension that must de facto replicate the original research and either substantiate it or call it into question. The problem in so many cases is an INSUFFICIENT SAMPLE SIZE. And the difficulty there is that getting a good sample is usually so expensive. I used to follow quite closely what was going on at the National Center for Complementary and Integrative Health (US) and at least they were honest enough in their testing of the effectiveness of such as Balboa Ginkgo Juice was that in the vast majority of cases, "more testing was required". Well what did you expect when you tested it on 34 people and only 27 completed the study? On a personal note. I once was part of a study that extended research that had demonstrated that having protein for breakfast enhanced your muscle strength. It was designed to show that having protein for your evening meal as well worked even better. The study involved providing me with free food for eight weeks, multiple daylong lab visits, supervised weight lifting and running, continuous blood sampling and, painful, muscle biopsies. ISTR there were about thirty participants divided between the real test group (I turned out to in that after the blinding was undone) and the control group. Oh, and they paid me a couple of hundred for my time. I would hazard a guess that the project grant was at least in the tens of thousands. The resulting paper got the study's leader her PhD and advanced the cause of science by an infinitesimal amount. The answer was that, yes, the hypothesis was proved within a small margin of error.
	__________________ "Reality is what's left when you cease to believe." Philip K. Dick

25th July 2022, 10:47 AM	#8
theprestige Penultimate Amazing Join Date: Aug 2007 Location: The Antimemetics Division Posts: 60,255	Originally Posted by Hellbound Yeah, that’s often forgotten. As I repeatedly tell my son, the reason we look for published scientific articles isn’t because they’re proof, in and of themselves. It’s because that’s really the start of the scientific investigation, so to speak. A paper should give all the info necessary for replication, and replication is really what determines if it’s a theory that should be accepted. Sent from my volcanic island lair using carrier pigeon. Originally Posted by Darat Problem is that it can be very difficult to get a grant for doing the same thing someone else has already done and published so what tends to happen is the "replication" has to come from "adjacent" research or drawn together by a metanalyses. Which raises all sorts of questions about scientific "truths" we take for granted. On the one hand, you have a perverse incentive to make sure your results are consistent with previous results. And on the other hand, you have a perverse incentive to not try replicating previous results.
	__________________ There is no Antimemetics Division.

25th July 2022, 03:22 PM	#9
casebro Penultimate Amazing Join Date: Jun 2005 Posts: 19,509	Maybe the researchers forgot what they came into the lab for.
	__________________ Any sufficiently advanced idea is indistinguishable from idiocy to those who don't actually understanding the concept.

25th July 2022, 07:57 PM	#10
Tero Master Poster Join Date: Oct 2010 Location: North American prairie Posts: 2,688	Throwing all that out does not exclude the amyloid plaques as part of the disease. https://en.wikipedia.org/wiki/Amyloid_plaques Their formation still needs to be studied, as well as intracellular proteins.
	__________________ Dominus vo-bisque'em Et cum spear a tu-tu, oh! Politics blog: https://esapolitics.blogspot.com/ Parody: http://karireport.blogspot.com/ Poll: https://projects.fivethirtyeight.com...proval-rating/

26th July 2022, 04:32 PM	#11
Lithrael Master Poster Join Date: Feb 2004 Posts: 2,376	Yeah, though this is a mess, the "16 years of research wasted because of faked paper" stuff is hyperbole. There's a good basic followup blog post also on Science. https://www.science.org/content/blog...t-does-it-mean "Lesné’s work now appears suspect across his entire publication record. AB56 itself does not seem to exist. Other researchers had failed to find it even in the first years after the 2006 publication, but that did not slow the beta-amyloid-oligomer field down at all. It was going to grow anyway, but it’s for sure that the AB56 stuff turbocharged it, too. Amyloid oligomers are a huge tangled area with all kinds of stuff to work on, and while no one could really prove that any particular oligomeric species was the cause of Alzheimer’s, no one could prove that there wasn’t such a causative agent, either, of course. It’s definitely fair to say that the Lesné work caused trials to happen more quickly and probably in greater number than they would have otherwise. Those trials have failed. But every single Alzheimer’s trial has failed. I think that any ultimate explanation of Alzheimer’s disease is going to have to include beta-amyloid as a big part of the story - but if attacking the disease from that standpoint is going to lead to viable treatments, we sure as hell haven’t been seeing it. We have to put money and effort down on other hypotheses and stop hammering, hammering, hammering on beta-amyloid so much. It isn’t working."
Lithrael Master Poster Join Date: Feb 2004 Posts: 2,376