The myth of Alzheimer's disease

 What happens when sixteen years of research is built on skewed data?


The house of cards collapsed. It started with a study of an experimental Alzheimer's drug called Simufilam. Lawsuits against pharmaceuticals are not necessarily unique. Recently, Zoloft has been criticized for promoting the idea that depression is caused by a chemical imbalance (it is not). But this case is different. It's not that the drug itself is fraudulent in its claims, it's probably based on fraudulent research.

For the past sixteen years, attempts to treat or cure the disease we know as Alzheimer's have been based on the apparent discovery of "patches and tangles" in patients' brains. Known as the amyloid hypothesis, it suggests that sticky clumps of the protein amyloid beta (Aβ) accumulate and cause disease. Uncovering the cause, of course, gives researchers new hope; if plaques become the target, then pharmaceutical intervention may be the answer. In 2006, a study by Sylvain Lesné from the University of Minnesota (UMN) published in Nature finally provided research support. Using mice and rats, Lensné's team found that artificially increasing Aβ led to a sharp decline in memory. Since the same protein was found in Alzheimer's patients, it appears that a causal link has been found.

Now these results are being questioned. The first to raise the alarm was Matthew Schrag, a neuroscientist and physician at Vanderbilt University who was brought in for a pharmaceutical case. This will be followed by a six-month review by Science, including image analysts and leading Alzheimer's researchers. They generally question hundreds of Lensny's images and even suggest that they have been combined or altered.

The investigation is ongoing and no official charges have yet been brought against the original research team, but the disturbing possibility is causing waves in the scientific community. Several drugs designed to help patients have been largely ineffective, and now we know why: They target a target that may not exist. But despite the headlines, this isn't the first time the plaque and tangle theory has been seriously challenged.

In 2007, I started working as the executive editor of Culture, Medicine and Psychiatry. I will be working under Editor-in-Chief Professor Atwood Gaines and often with Editorial Board Member, MD-PhD and Professor of Neurology and Neuroscience Peter Whitehouse. I started my term in June; at the beginning of my university semester I had already heard about what Whitehouse called the "myth" of Alzheimer's disease. It begins with the story of a 50-year-old woman in turn-of-the-century Germany.

His name is Auguste Deter. Her husband took her to the Community Hospital for Mental and Epileptic Patients in Frankfurt. Auguste doesn't remember anything. Small things first, then important things. He was afraid of people, felt constantly paranoid and confused, and eventually became too aggressive for his partner to handle. Auguste is admitted to a psychiatric hospital - but not before meeting a young doctor named Alois Alzheimer.

Alzheimer's recognizes him in life and in death; his brain will be sent for an autopsy. Under the microscope, he saw what we now call amyloid plaques and neurofibrillary tangles—plaques are distinct clumps of Aβ. After he published his findings, the disease was named after him, and earlier descriptions (such as senile dementia) were soon grouped under the umbrella. Plaques seem to be in the brains of most sufferers, so something is wrong with the proteins, but no one knows what or why. Some theories postulate disrupted neurotransmitters (cholinergic hypothesis), others tau protein abnormalities causing blockage of nutrients and other inflammation, metabolic function and lifestyle choices. But after the original 2006 documentary, Aβ won the day. For a hundred years, memory problems in old age have been diseases with a cause.

It's just not true.

"Despite the widespread belief that there is a disease called Alzheimer's that science is at war with," Whitehouse explained, "Alzheimer's is indistinguishable from normal aging, and no two courses of the disease are the same." That doesn't mean people don't suffer. We have incontrovertible evidence that some people suffer from rapid mental decline along with many other disturbing symptoms. But there is no, says Whitehouse, biological profile. There is no way to predict the chances, not even genetically, because some people in the same family will have it - but not all - and no one is the same. No one "gets" the unique disease called Alzheimer's, he explained. We acquire constellations of conditions, each influencing the other and having many connections to our living conditions, support, health and care.

So what is it? I asked honestly; I consider Alzheimer's disease to be one of the scariest diseases - for myself or for someone close to me. His answer surprised me. Brain aging, he told me. To cure it, "we have to stop the brain's natural aging process."

I had a hard time swallowing at first. I witnessed the progression of so-called Alzheimer's disease through the deterioration of a friend's parent. It's not like normal aging for me. What went wrong? Why is it accelerated? Why does it include other symptoms such as aggression? Whitehouse's proposal initially felt that these experiences were being denied; in reality, however, his work is concerned with how we try to homogenize aging—box it, treat it as pathological. Things are not right in the brain. People can decay at an alarming rate. The cause, like individual people, is complex, interconnected, multiple and unique.

Whitehouse has worked in the field of aging and Alzheimer's disease for more than 40 years. However, when drugs came on the market, the biological approach to brain aging changed from caring for the whole patient—consultation with the family, ensuring quality of life, support—to using drugs. "Too often," he wrote in his book The Myth of Alzheimer's Disease, "patients and their families leave the doctor's office with just a prescription pill" without knowing how to treat the condition. What we need, he suggests, is to rethink what aging means to the unique, individual brain, and what kind of support makes life meaningful wherever we are. is on the aging spectrum.

That was in 2008, two years after the Lensný investigation. Now, in 2022, when the Aβ hypothesis begins to fall, I will return to Whitehouse's ideas about Alzheimer's not as one disease but many - and about brain aging as something to be treated with care and not pills (and stigma).

I want a drug to stop Alzheimer's. I want the disease itself to be unique, easy to target, and easy to defeat. We want monsters with faces because we can make the necessary silver bullet. When it comes to potentially fraudulent data, "the immediate, obvious damage is wasted NIH funding and wasted thinking," said Stanford University Nobel Prize-winning neuroscientist Thomas Südhof. In this report in Science [by Joseph Ross], the NIH spent $1.6 billion a year funding amyloid research; also suggest that scientists developing other causes of Alzheimer's disease (immune dysfunction, inflammation, etc.) "claim to be sidelined by the 'amyloid mafia'." And all of this brought me back to the work of Peter Whitehouse and my first odd look at a different way of thinking.

Imagine what we could achieve if sixteen years of funding were devoted to the right kind of brain aging research? Consider funding used to remove the stigma surrounding dementia in general, teaching family members and society as a whole how to provide supportive care. It's an excellent reminder that science can sometimes go too far. We must always explore the potential for healing and healing. However, we must also perceive the wider world around us and realize that singular solutions only work for individual problems. And nothing about Alzheimer's and the aging brain is that simple.

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