By targeting a hidden toxic protein, an experimental drug could change how Alzheimer’s is prevented and treated.
For decades, Alzheimer’s disease has been treated as a condition that becomes visible only when memory begins to fail. Now, new research from Northwestern University challenges that idea, suggesting the disease may quietly begin years, even decades, before symptoms appear.
In a study published this month in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association, scientists identified a previously unknown toxic protein in the brain that appears to trigger the earliest stages of Alzheimer’s. More strikingly, an experimental drug was able to stop this early damage in mice when given before memory loss began.
The findings point to a potential shift in how the disease is approached: from managing symptoms to preventing damage before it starts.
The research team discovered a particularly harmful form of amyloid beta, a protein long associated with Alzheimer’s, that behaves differently from those studied before. Rather than forming large plaques later in the disease, this subtype appears early, inside stressed neurons and on nearby support cells called astrocytes [1].
“These early events are happening long before memory loss is apparent,” said Daniel Kranz, the study’s first author. “By the time symptoms emerge, the underlying pathology is already advanced.”
Astrocytes normally protect neurons and help regulate inflammation. But when exposed to this toxic protein, they become overactive, triggering inflammation that can spread across the brain. This inflammatory response is increasingly seen as a key driver of neurodegeneration.
The experimental drug, known as NU-9, was designed to prevent toxic protein buildup inside brain cells. In the new study, researchers gave NU-9 daily to mice genetically predisposed to Alzheimer’s, before any cognitive symptoms appeared [2].
After 60 days, the results were notable. The drug significantly reduced brain inflammation, lowered levels of the toxic protein, and sharply decreased an abnormal form of another protein linked to cognitive decline. These improvements were seen across multiple brain regions, suggesting a broad protective effect.
“These results are stunning,” said William Klein, a Northwestern neurobiology professor and co-author of the study. “NU-9 had an outstanding effect on early neuroinflammation, which is closely linked to the start of the disease.”
Many Alzheimer’s drug trials have failed, in part because they intervene too late, after neurons have already been damaged or lost. NU-9 was tested during what researchers call the “pre-symptomatic window,” a period when the disease is active but silent.
That timing could be critical. By blocking the earliest toxic processes, the drug may prevent the chain reaction that ultimately leads to memory loss and cognitive decline.
Kranz likened the strategy to preventive care in other chronic diseases. “If you catch the disease early enough, you have a much better chance of stopping it,” he said.
NU-9 is not new to neurodegenerative research. Originally developed over 15 years ago, the compound has already shown promise in animal models of amyotrophic lateral sclerosis (ALS). In 2024, it received clearance from the US Food and Drug Administration to begin human trials for ALS.
Earlier this year, the same team demonstrated that NU-9 could clear toxic amyloid proteins in lab-grown brain cells related to learning and memory. The new findings build on that work by showing the drug’s ability to prevent early damage in living brains.
“Cells have natural systems to clear toxic proteins, but those systems break down in diseases like Alzheimer’s,” Klein explained. “NU-9 appears to rescue that protective pathway.”
The researchers see NU-9 as part of a broader shift toward preventive treatment. Blood tests that detect early signs of Alzheimer’s are already in development, raising the possibility of identifying at-risk individuals long before symptoms appear.
“Most people understand managing cholesterol to prevent heart attacks,” said Richard Silverman, the chemist who invented NU-9. “NU-9 could play a similar role for Alzheimer’s.”
The team is now testing the drug in additional models that more closely reflect typical human aging, and is tracking whether treated animals go on to develop memory problems over time.
While human trials for Alzheimer’s are still ahead, the study adds momentum to a growing idea in longevity science: that neurodegenerative diseases may be slowed – or even stopped – if treated early enough.
[1] https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70968
[2] https://www.sciencedaily.com/releases/2025/12/251222080119.htm
