Recently discovered genetic variants seem to protect against Alzheimer’s disease, suggesting a path toward a cure. But are their powers believable? Meagan Cantwell, a senior video producer at Science, explains. #ScienceTok #STEMTok #NewsFromScience CREDITS: (PHOTOS) FEDERICO RIOS/THE NEW YORK TIMES/REDUX; TONY LUONG; (VIDEO PRODUCTION) M. CANTWELL/SCIENCE

One of the most talked about Alzheimer's discoveries from the past decade might be unraveling. The work started in Colombia in the 1980s, when researchers discovered hundreds of patients who suffered from dementia starting in their late 40s. They eventually discovered that many of them, members of a large extended family, had a genetic mutation that caused them to develop early Alzheimer's disease. They named the mutation Paesa after a nickname for the people of the Antiochia region of Colombia. The gene is involved in the production of a protein amyloid beta, which is widely thought to set off a cascade of biochemical events that kill brain cells and cause dementia. But in 2019, the researchers announced that they had found a woman named Alidia, who had the Paesa mutation, but didn't experience memory loss until her 70s, decades later than her relatives. Leading the charge on this discovery were a married pair of researchers, named Joseph Arboleda Velasquez and Yakil Kiros. They found that Alirius' protection against Alzheimer's came down to having two copies of a single gene mutation known as Christchurch. The discovery attracted a ton of attention, and there was more excitement when the team identified another gene variant that appeared to protect people with the Paesa mutation. They've received millions of dollars in funding to follow up on these discoveries. But some in the field have questioned whether a single mutation could really explain why these people were protected against Alzheimer's. Scientists, reporters Charles Pillar and Jenny Aaron Smith teamed up to investigate. They enlisted the help of three forensic image experts, and on spotted images and research papers authored by the group, that seemed to be improperly altered or copied. Here's a 2024 paper published in Frontiers in Molecular Neuroscience that claims that the Christchurch mutation helps neuron survive. Researchers inserted the mutation into brain organoids, which are structures that mimic some brain functions, from a Colombian person with early onset Alzheimer's, and compared them to organoids from Aliria. Each column should represent different organoids, yet multiple parts of the figure appear to be duplicated across columns. It could come from an unlikely series of errors, or it could indicate an improper attempt to support the paper's hypothesis. The researchers didn't provide the original high-resolution images to tease out what actually happened here, and there's another line of work that's also raised concern. While Aliria had both copies of the Christchurch mutation, researchers wanted to see if just one copy would also delay the onset of symptoms. Initial studies didn't seem to support this. A 2023 study led by Nicholas Cochran, named over a dozen variants that could impact the age of Alzheimer's onset in price and mutation carriers. Christchurch wasn't one of them. But later that year, Keidol's displayed data at a conference, showing that 12 pi-secureus with just one copy of Christchurch were symptom-free between four to seven years longer than those without the mutation. Cochran was surprised. He recognized most of these patients from his own research, and noticed that for some, the age of disease onset had been changed, and now showed patients developing symptoms later. When Cochran wrote to Keidol's asking why, she said that the patient data was updated based on new standards, and to correct past inconsistencies or errors. Her team's new findings were published in the New England Journal of Medicine, and Cochran published a response questioning those findings. Science asked clinicians familiar with some of those cases to review the changes, and they didn't see them as justified. But the theory marched on, and some researchers even launched drug development efforts based on the Christchurch findings. The Christchurch mutation might still turn out to be relevant, possibly in combination with other genes, and researchers outside of the group have found some pretty intriguing biological effects in mice, as well as human brain cell cultures. But that doesn't necessarily mean that it'll protect against Alzheimer's. The range of problems explored in science's investigation raises doubt into its potential.