# Blood brain barrier and Alzheimer's **URL:** \ **Category:** Miscellaneous and Personal Stuff I Must Share\ **Created:** [May 3, 2021, 5:11pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307 "2021-05-03T17:11:35Z")\ **Posts on this page:** 18\ **Page:** 1
**Author:** ![Hari\_Seldon](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/hari_seldon/32/5173_2.png) [@Hari\_Seldon](https://boards.straightdope.com/u/Hari_Seldon)\ **Post date:** [May 3, 2021, 5:11pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/1 "2021-05-03T17:11:35Z")
There is a fascinating article in this month’s Scientific American. There is no point in linking to it since it is behind a paywall. But I will try to summarize the salient features. It describes a series of experiments carried out on mice (and so the tentative conclusions may be of more interest to the mice among you) 1. The first experiments demonstrated that extreme stress can cause holes to develop in the blood brain barrier (BBB). They were motivated by evidence in Gulf War I veterans. 2. The next series showed that blood in the brain led to Alzheimer-like symproms (which I will call, for this post only, ALS). 3. The next series examined each component of the blood and showed that the one that led to ALS was albumin. 4. The next series showed that the albumin bonded to a kind of neuron called an astrocyte, eventually resulting in brain inflammation and ALS. 5. The next experiment was to breed some GMO mice whose astrocytes lacked the receptor that bonded to albumin. These mice did not develop ALS in response to albumin. The article does not mention if blocking those receptors had any other significant effects. 6. It turned out there was an already known drug (called IPW) that specifically blocks that receptor on the astrocyte. The next experiments consisted in treating\* the mice with IPW. Not only did this block the ALS in mice, it reversed, to some extent although not completely, the ALS in mice that had already shown signs of dementia. And the article essentially stopped there. Although it mentioned that the two authors plus the man who told them about the IPW, had formed a company. \*Treated how? Doesn’t say. Do you have to open the brain case and spray it in? Or inject it and assume it can get to the brain through the holes in the BBB? Or swallow it? Side effects? It was originally an anti-cancer drug, so even serious side effects might be acceptable. ---
**Author:** ![Omar\_Little](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/omar_little/32/269_2.png) [@Omar\_Little](https://boards.straightdope.com/u/Omar_Little)\ **Post date:** [May 3, 2021, 9:50pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/2 "2021-05-03T21:50:10Z")
> **[Can We Cure Dementia? - Cal Alumni Association](https://alumni.berkeley.edu/california-magazine/summer-2020/can-we-cure-dementia)** > > Daniela Kaufer has reversed the effects of aging in mouse brains. Can she do it in humans? IT ALL STARTED WITH A MYSTERIOUS ILLNESS. In the 1990s, thousands of U.S. veterans returning from combat in the Persian Gulf began suffering from what became... Article form June 2020 on the same drug and potential impact on Alzheimers. " **TO DEVELOP A DRUG TO TREAT HUMANS,** Kaufer, Friedman, and Hart have since started a company, Mend Neuroscience. Though shelter-in-place has thrown a wrench in their timeline, Kaufer hopes the company can start clinical trials in a few years." “She tries to respond to every email, but she knows that she’s **years away** from clinical trials, let alone FDA approval and a market-ready therapy.” ---
**Author:** ![PastTense](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/pasttense/32/14550_2.png) [@PastTense](https://boards.straightdope.com/u/PastTense)\ **Post date:** [May 4, 2021, 2:55am UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/3 "2021-05-04T02:55:18Z")
Basically lots of articles in Scientific American summarize scientific articles published in scientific/scholarly journals. Hari, perhaps you could check the bibliography and find some of these which may be publicly available. Here is one possibility: [https://stm.sciencemag.org/content/11/521/eaaw8954.full](https://stm.sciencemag.org/content/11/521/eaaw8954.full) ---
**Author:** ![Hari\_Seldon](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/hari_seldon/32/5173_2.png) [@Hari\_Seldon](https://boards.straightdope.com/u/Hari_Seldon)\ **Post date:** [May 4, 2021, 4:48pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/4 "2021-05-04T16:48:46Z")
Unlike most Sci-Am articles, there are no references. The authors are Daniela Kaufer and Alon Friedman so you could search for their papers. If their hypothesis is correct, that would explain why drugs that clear beta-amyloid have been totally useless for Alzheimer’s. ---
**Author:** ![Treppenwitz](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/treppenwitz/32/3445_2.png) [@Treppenwitz](https://boards.straightdope.com/u/Treppenwitz)\ **Post date:** [May 4, 2021, 8:15pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/5 "2021-05-04T20:15:05Z")
> [@Hari\_Seldon](#): > > IPW Did the article specify if the drug was IPW-5371? I was curious enough to try to track it down. It’s turning into quite the rabbit hole. For instance: > Given the probable involvement of TGF-β in the progression of **COVID-19** , a preclinical, anti-TGFβ receptor 1 product, **IPW5371** (Innovation Pathways, Palo Alto, CA) may also be a promising candidate to treat COVID-19-induced lung fibrosis, as it has previously been shown to reduce fibrosis and improve survival in a mouse model of radiation exposure [Source](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861125/). My bold. There will be people on these boards who are far better qualified to explain what’s happening here than I am; but you do see spurts of interest in the way a new drug impacts biological pathways, and then that fans out to preclinical testing in a range of disease conditions - sometimes because there’s an obvious lead, sometimes because there’s a hot topic of interest (COVID would qualify). It can feel a bit like a solution looking for a problem - not that that is necessarily a bad thing. j ---
**Author:** ![Hari\_Seldon](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/hari_seldon/32/5173_2.png) [@Hari\_Seldon](https://boards.straightdope.com/u/Hari_Seldon)\ **Post date:** [May 4, 2021, 10:08pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/6 "2021-05-04T22:08:26Z")
You may have it. Here is the relevant sentence from the article: > Barry Hart, a medicinal chemist at Innovation Pathways, a start-up drug company in Palo Alto, Calif., had designed an anticancer drug that specifically blocked the activity of the TGFβ receptor. Hart contacted us and suggested that we try the drug, called IPW, on our mice. The TGF-beta receptor in the astrocyte was the receptor that bonded to the albumin. Note the company Innovation Pathways. As a subscriber, I was able to download the article, but of course I cannot post it. ---
**Author:** ![Hari\_Seldon](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/hari_seldon/32/5173_2.png) [@Hari\_Seldon](https://boards.straightdope.com/u/Hari_Seldon)\ **Post date:** [May 5, 2021, 1:22pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/7 "2021-05-05T13:22:31Z")
My daughter was able to get the link: > **[Damage to a Protective Shield around the Brain May Lead to Alzheimer’s and...](https://www.scientificamerican.com/article/damage-to-a-protective-shield-around-the-brain-may-lead-to-alzheimers-and-other-diseases/)** > > The blood-brain barrier deteriorates with aging, but animal studies indicate repairs can make old brains look young again But she used to work for Nature which is affiliated with Sci-Am so her computer may automatically link. I am interested to know if this works for others. ---
**Author:** ![Treppenwitz](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/treppenwitz/32/3445_2.png) [@Treppenwitz](https://boards.straightdope.com/u/Treppenwitz)\ **Post date:** [May 5, 2021, 5:57pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/8 "2021-05-05T17:57:09Z")
Yep, the link works. Interesting read. I’m pretty sure the (early!) investigative drug must be IPW-5371. j ---
**Author:** ![JohnT](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/johnt/32/15048_2.png) [@JohnT](https://boards.straightdope.com/u/JohnT)\ **Post date:** [July 23, 2022, 12:48pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/9 "2022-07-23T12:48:25Z")
> [@Hari\_Seldon](#): > > If their hypothesis is correct, that would explain why drugs that clear beta-amyloid have been totally useless for Alzheimer’s. Well, some news about _that_: > [@](#): > > Over the last two decades, Alzheimer’s drugs have been notable mostly for having[a 99% failure rate in human trials](https://www.beingpatient.com/alzheimers-drug-trials-failure-rate/). It’s not unusual for drugs that are effective in vitro and in animal models to turn out to be less than successful when used in humans, but Alzheimer’s has a record that makes the batting average in other areas look like Hall of Fame material. > > And now we have a good idea of why. _ **Because it looks like the original paper that established the amyloid plaque model as the foundation of Alzheimer’s research over the last 16 years might not just be wrong, but a deliberate fraud…** _ > > Should this fraud turn out to be as extensive as it appears at first glance, the implications go well beyond just misdirecting tens of billions in funding and millions of hours of research over the last two decades. Since that 2006 publication, the presence or absence of this specific amyloid has often been treated as _diagnostic_ of Alzheimer’s. Meaning that patients who did die from Alzheimer’s may have been misdiagnosed as having something else. > **[Two decades of Alzheimer's research may be based on deliberate fraud that has...](https://www.dailykos.com/stories/2022/7/22/2111914/-Two-decades-of-Alzheimer-s-research-may-be-based-on-deliberate-fraud-that-has-cost-millions-of-lives)** > > Last month, drug company Genentech reported on the first clinical trials of the drug crenezumab, a drug targeting amyloid proteins that form sticky plaques in the brains of Alzheimer’s disease patients. The drug had been particularly effective in... Original _Science_ article: [https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease](https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease) ---
**Author:** ![Jackmannii](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/jackmannii/32/311_2.png) [@Jackmannii](https://boards.straightdope.com/u/Jackmannii)\ **Post date:** [July 23, 2022, 12:57pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/10 "2022-07-23T12:57:59Z")
I read that _Science_ article yesterday. Fascinating (as Mr. Spock would say). There should be massive repercussions if (as seems likely) a great deal of time, effort and money was spent investigating a hypothesis founded on fabrication. Genuinely intriguing pathways toward preventing and successfully treating dementia should be followed. The number of false trails taken in researching Alzheimer’s, though, is sobering. ---
**Author:** ![JohnT](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/johnt/32/15048_2.png) [@JohnT](https://boards.straightdope.com/u/JohnT)\ **Post date:** [July 23, 2022, 12:59pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/11 "2022-07-23T12:59:04Z")
The author has a tweet thread where he goes into the fallout since publication: > ---
**Author:** ![JohnT](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/johnt/32/15048_2.png) [@JohnT](https://boards.straightdope.com/u/JohnT)\ **Post date:** [July 23, 2022, 1:41pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/12 "2022-07-23T13:41:02Z")
Almost getting to the point where I find foundational destruction of public trust to be one of the worst crimes imaginable in a civil society: arguably much worse than a singular count of murder and further reaching in its harms. ---
**Author:** ![Bootb](https://avatars.discourse-cdn.com/v4/letter/b/e19b73/32.png) [@Bootb](https://boards.straightdope.com/u/Bootb)\ **Post date:** [July 23, 2022, 2:09pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/13 "2022-07-23T14:09:25Z")
> [@Jackmannii](#): > > Genuinely intriguing pathways toward preventing and successfully treating dementia should be followed. The number of false trails taken in researching Alzheimer’s, though, is sobering. The silver lining is that now we have a great deal of knowledge about what **doesn’t** work. When doing science, negative results can be equally as important as positive results, although human nature tends to **not** feel that way about it. This body of knowledge that we have accumulated may inform decisions about other lines of inquiry. ---
**Author:** ![Hari\_Seldon](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/hari_seldon/32/5173_2.png) [@Hari\_Seldon](https://boards.straightdope.com/u/Hari_Seldon)\ **Post date:** [July 24, 2022, 11:44pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/14 "2022-07-24T23:44:23Z")
What astonishes me is that a year and a quarter later, there has still been no publicity for the original Sci-Am article. Nor have I heard of any studies based on that drug. Especially since the fraud seems to have been exposed. ---
**Author:** ![PastTense](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/pasttense/32/14550_2.png) [@PastTense](https://boards.straightdope.com/u/PastTense)\ **Post date:** [July 27, 2022, 2:13am UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/15 "2022-07-27T02:13:50Z")
> [@Jackmannii](#): > > I read that _Science_ article yesterday. Fascinating (as Mr. Spock would say). There should be massive repercussions if (as seems likely) a great deal of time, effort and money was spent investigating a hypothesis founded on fabrication. See this article: > \*_Did the 56 Work Lead to Clinical Trials?_ > > That’s a question that many have been asking since this scandal broke a few days ago. And the answer is that no, I have been unable to find a clinical trial that specifically targeted the AB\*56 oligomer itself (I’ll be glad to be corrected on this point, though). What there have been are trials that (to a [greater or lesser extent](https://pubmed.ncbi.nlm.nih.gov/32787971/)) tried to target the whole amyloid-oligomer hypothesis in general, but I have to think that those would have happened anyway. [https://www.science.org/content/blog-post/faked-beta-amyloid-data-what-does-it-mean](https://www.science.org/content/blog-post/faked-beta-amyloid-data-what-does-it-mean) ---
**Author:** ![Jackmannii](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/jackmannii/32/311_2.png) [@Jackmannii](https://boards.straightdope.com/u/Jackmannii)\ **Post date:** [July 27, 2022, 2:32am UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/16 "2022-07-27T02:32:22Z")
The problem goes well beyond holding clinical drug trials. “Schrag’s discovery has massive financial implications. “The immediate, obvious damage is wasted NIH funding and wasted thinking in the field because people are using these results as a starting point for their own experiments,” commented neuroscientist, Nobel laureate and Alzheimer’s expert Thomas Südhof ([Stanford University](https://www.stanford.edu/), CA, USA).” [https://www.biotechniques.com/neuroscience/most-cited-and-most-notorious-how-the-2006-alzheimers-paper-potentially-misled-research/](https://www.biotechniques.com/neuroscience/most-cited-and-most-notorious-how-the-2006-alzheimers-paper-potentially-misled-research/) ---
**Author:** ![Earl\_Snake-Hips\_Tucker](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/earl_snake-hips_tucker/32/3269_2.png) [@Earl\_Snake-Hips\_Tucker](https://boards.straightdope.com/u/Earl_Snake-Hips_Tucker)\ **Post date:** [July 27, 2022, 1:31pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/17 "2022-07-27T13:31:13Z")
So, help with the short version of the issue (so that we uninformed folks don’t have to track down all the links): Is the fraud that the amyloid plaques are not indicators of ALZ or is it something else? Side question: If ALZ drugs are 99% ineffective. . . what’s the point in prescribing them, and do any drugs actually mitigate or inhibit the progression? ---
**Author:** ![Bootb](https://avatars.discourse-cdn.com/v4/letter/b/e19b73/32.png) [@Bootb](https://boards.straightdope.com/u/Bootb)\ **Post date:** [July 27, 2022, 2:02pm UTC](https://boards.straightdope.com/t/blood-brain-barrier-and-alzheimers/941307/18 "2022-07-27T14:02:25Z")
> [@Earl\_Snake-Hips\_Tucker](#): > > Is the fraud that the amyloid plaques are not indicators of ALZ or is it something else? The issue has been reported in such a way that somebody who only marginally pays attention would probably assume that the plaques are the cause of Alzheimer’s. But at least some of those who have paid a little bit more attention know that the link remains a mystery.