Researchers at the University of California, Riverside are offering a new way to think about how Alzheimer’s disease may begin. In a study published in Proceedings of the National Academy of Sciences, Nexus, the team suggests the disease may be triggered not only by protein plaques in the brain, but by interference between two proteins inside nerve cells.
For decades, Alzheimer’s research has focused heavily on amyloid beta, or a-beta, which forms clumps in the brains of patients. That focus was supported by inherited mutations that raise a-beta levels and can cause early onset disease. However, many trials aimed at clearing a-beta have not halted or reversed Alzheimer’s progression. Researchers have also known that tau, another protein, accumulates in patients’ brains, but the relationship between the two has remained unclear.
The UCR study centers on microtubules, small structures that help move materials through neurons. Tau normally stabilizes these structures. The researchers found that the part of tau that binds to microtubules resembles a-beta in size and structure. Using fluorescent labeling, they reported that a-beta can also bind to microtubules and does so with strength similar to tau.
This finding led the team to propose that when a-beta builds up inside neurons, it may compete with tau for the same binding sites. If tau is displaced, microtubules may lose stability, disrupting the cell’s internal transport system. Tau may then clump or move into parts of neurons where it is not normally found.
The theory may also align with aging-related declines in autophagy, the cellular process that clears unwanted proteins. If cells remove less a-beta over time, the protein could accumulate internally. Future research will need to test the model, but it could shift treatment strategies toward protecting microtubules or improving protein clearance, rather than focusing only on removing plaques outside cells.