Alzheimer’s disease, the most common form of dementia, affects more than 50 million people worldwide.
For decades, researchers have known that two proteins—tau and amyloid-β—play central roles in the disease.
Tau forms tangles inside brain cells, while amyloid-β builds plaques between them. Both contribute to the loss of healthy neurons.
Until now, however, scientists have not fully understood whether these two proteins interact directly or how that interaction might influence the disease.
A Korean research team, working with international collaborators, has now shown for the first time at the molecular level that tau and amyloid-β can indeed communicate with one another.
Remarkably, their interaction can reduce the harmful effects of amyloid-β, shifting its behavior toward less toxic forms.
The study, led by Professor Mi Hee Lim at KAIST, was published in Nature Chemical Biology.
Tau normally helps transport nutrients and signals inside neurons, while amyloid-β is a fragment of a larger protein involved in brain development and cell signaling.
In Alzheimer’s, both proteins go awry: tau forms twisted fibers called neurofibrillary tangles, and amyloid-β accumulates into sticky clumps known as plaques.
Though these structures occur in different locations within the brain, scientists have long suspected that tau and amyloid-β may interact. The new study finally provides direct evidence of this interaction and its effects.
The researchers found that specific regions of tau, known as microtubule-binding repeats, can bind to amyloid-β.
When this happens, instead of forming its usual rigid, highly toxic fibrils, amyloid-β takes an alternate path, creating softer, less harmful aggregates.
In effect, tau can delay the earliest steps of amyloid aggregation and change how quickly and in what form it builds up. This shift reduces amyloid’s toxicity both inside and outside brain cells.
To uncover this mechanism, the team used a wide range of analytical tools, including spectroscopy, mass spectrometry, calorimetry, and nuclear magnetic resonance, combined with cell-based toxicity tests. Their findings showed that the chemical properties of tau—its balance of water-attracting and water-repelling regions—determine how well it binds amyloid-β and how effectively it can alter the protein’s toxic behavior.
“This research uncovers a new molecular mechanism for how dementia begins and progresses,” said Dr. Young-Ho Lee of the Korea Basic Science Institute.
“It also highlights how studying molecular interactions between proteins could provide insights not only into Alzheimer’s, but into other conditions such as Parkinson’s, diabetes, and even cancer.”
Professor Lim added that tau is not just a harmful protein contributing to tangles. Under certain conditions, it has an active protective role by reducing amyloid-β toxicity. “This discovery provides a new turning point in understanding Alzheimer’s disease,” she said.
“Identifying these molecular interactions could lead to new biomarkers for diagnosis and therapeutic targets for a wide range of neurodegenerative brain disorders.”
If you care about Alzheimer’s disease, please read studies about root cause of Alzheimer’s disease and new treatment and Scientists find the link between eye disease glaucoma and Alzheimer’s disease.
For more health information, please read studies about new way to treat Alzheimer’s disease and Fluctuating cholesterol and triglyceride levels are linked to Alzheimer’s disease.
