Tea at Trianon: One of the Driving Forces of Alzheimer’s Disease

John Wilson Croker on Marie-Antoinette

"We have followed the history of Marie Antoinette with the greatest diligence and scrupulosity. We have lived in those times. We have talked with some of her friends and some of her enemies; we have read, certainly not all, but hundreds of the libels written against her; and we have, in short, examined her life with– if we may be allowed to say so of ourselves– something of the accuracy of contemporaries, the diligence of inquirers, and the impartiality of historians, all combined; and we feel it our duty to declare, in as a solemn a manner as literature admits of, our well-matured opinion that every reproach against the morals of the queen was a gross calumny– that she was, as we have said, one of the purest of human beings."

~from History of the Guillotine by John Wilson Croker, 1844

Edmund Burke on Marie-Antoinette

"It is now sixteen or seventeen years since I saw the queen of France, then dauphiness, at Versailles; and surely there never lighted on this orb, which she hardly seemed to touch, a more delightful vision. I saw her just above the horizon, decorating and cheering the elevated sphere she had just begun to move in, glittering like a morning star full of life and splendor and joy. Oh, what a revolution....Little did I dream that I should have lived to see such disasters fall upon her, in a nation of gallant men, in a nation of men of honor and of cavaliers! I thought ten thousand swords must have leaped from their scabbards, to avenge even a look which threatened her with insult. But the age of chivalry is gone; that of sophisters, economists, and calculators has succeeded...."

~Edmund Burke, October 1790

Tuesday, August 2, 2022

One of the Driving Forces of Alzheimer’s Disease

From SciTech Daily:

Now, new research from Flinders University has demonstrated how a protein called tau, which is a critical factor in the development of Alzheimer’s disease, turns from normal to a disease state. Furthermore, the study reveals how this discovery could deliver a therapeutic target.

Published on July 6, 2022, in the journal Science Advances, the team’s findings provide hope for preventing the tau transformation process from happening, thereby maintaining tau in a healthy state and avoiding damaging consequences on brain cells.

“Alongside a small peptide called amyloid-beta, the tau protein is a central factor in Alzheimer’s disease. Tau is necessary for the toxic effects on brain cells that then result in impaired memory function,” says senior study author Dr. Arne Ittner, Senior Research Fellow in Neuroscience in the Flinders Health and Medical Research Institute. (Read more.)

From Science:

In August 2021, Matthew Schrag, a neuroscientist and physician at Vanderbilt University, got a call that would plunge him into a maelstrom of possible scientific misconduct. A colleague wanted to connect him with an attorney investigating an experimental drug for Alzheimer’s disease called Simufilam. The drug’s developer, Cassava Sciences, claimed it improved cognition, partly by repairing a protein that can block sticky brain deposits of the protein amyloid beta (Aβ), a hallmark of Alzheimer’s. The attorney’s clients—two prominent neuroscientists who are also short sellers who profit if the company’s stock falls—believed some research related to Simufilam may have been “fraudulent,” according to a petition later filed on their behalf with the U.S. Food and Drug Administration (FDA).

Schrag, 37, a softspoken, nonchalantly rumpled junior professor, had already gained some notoriety by publicly criticizing the controversial FDA approval of the anti-Aβ drug Aduhelm. His own research also contradicted some of Cassava’s claims. He feared volunteers in ongoing Simufilam trials faced risks of side effects with no chance of benefit.

So he applied his technical and medical knowledge to interrogate published images about the drug and its underlying science—for which the attorney paid him $18,000. He identified apparently altered or duplicated images in dozens of journal articles. The attorney reported many of the discoveries in the FDA petition, and Schrag sent all of them to the National Institutes of Health (NIH), which had invested tens of millions of dollars in the work. (Cassava denies any misconduct [see sidebar, below].)

But Schrag’s sleuthing drew him into a different episode of possible misconduct, leading to findings that threaten one of the most cited Alzheimer’s studies of this century and numerous related experiments.

The first author of that influential study, published in Nature in 2006, was an ascending neuroscientist: Sylvain Lesné of the University of Minnesota (UMN), Twin Cities. His work underpins a key element of the dominant yet controversial amyloid hypothesis of Alzheimer’s, which holds that Aβ clumps, known as plaques, in brain tissue are a primary cause of the devastating illness, which afflicts tens of millions globally. In what looked like a smoking gun for the theory and a lead to possible therapies, Lesné and his colleagues discovered an Aβ subtype and seemed to prove it caused dementia in rats. If Schrag’s doubts are correct, Lesné’s findings were an elaborate mirage.

Schrag, who had not publicly revealed his role as a whistleblower until this article, avoids the word “fraud” in his critiques of Lesné’s work and the Cassava-related studies and does not claim to have proved misconduct. That would require access to original, complete, unpublished images and in some cases raw numerical data. “I focus on what we can see in the published images, and describe them as red flags, not final conclusions,” he says. “The data should speak for itself.” (Read more.)