A new study is raising questions about one of the most widely held ideas in Alzheimer’s research—suggesting the disease may not start with plaques in the brain after all.
Researchers at the University of California, Riverside (UCR) say the earliest changes could instead happen inside nerve cells, where two key proteins appear to interfere with each other.
For years, much of the focus has been on amyloid beta, or a-beta, because it forms clumps in the brains of people with Alzheimer’s. That link appeared well supported, especially since genetic mutations that increase a-beta levels are known to cause early-onset forms of the disease.
Michael Kane, chief medical officer at Indiana Center for Recovery, told Newsweek that the findings of this study should not be seen as dismissing the amyloid theory entirely, but rather as refining it.
“I see these findings less as a rejection of the amyloid theory and more as a possible link between amyloid beta and tau,” he said.
Connection Between Amyloid Beta and Tau
Scientists have long known that another protein, tau, is also involved. Both a-beta and tau build up in the brains of people diagnosed with Alzheimer’s, yet how they are connected has remained unclear.
“In addition to having dementia, Alzheimer’s diagnosis requires both a-beta and tau buildup in the brain,” said study lead author Ryan Julian, a chemistry professor at UCR. “But many labs focus on the role of one and ignore the other.”
The new study, published in Proceedings of the National Academy of Sciences, Nexus, looks at what happens when the two proteins are present inside the same cell.
Kane said this connection is one of the most significant aspects of the research.
“Amyloid beta and tau have both been central to Alzheimer’s research for decades, but the field has struggled to explain exactly how they interact. This study gives scientists a more specific place to look,” he said.
What Happens Inside Nerve Cell
Tau normally supports structures called microtubules, which act as internal pathways, helping nerve cells move essential materials to where they are needed.
The researchers found that the part of tau that attaches to these structures is very similar to amyloid beta. That similarity led them to examine whether a-beta could attach to microtubules in the same way.
Using a fluorescent marker to track the protein, the team observed that a-beta can bind to microtubules with similar strength to tau.
“Our work shows amyloid beta and tau compete for the same binding sites on microtubules, and that a-beta can prevent tau from functioning correctly,” Julian said.
Kane said this mechanism could represent an earlier stage of disease development than previously recognised.
“The damage may start earlier, with the cell’s machinery becoming less stable,” he said.
Disruption That May Come First
The researchers suggest that this competition could be an important early step.
If a-beta builds up inside a neuron, it may push tau away from the microtubules. Without tau in place, the cell’s transport system may begin to break down.
At the same time, tau may start to change behavior—clumping together and moving into areas of the cell where it is not normally found.
This points to a different way of thinking about the disease. Instead of protein buildup being the starting cause on its own, the two processes may be part of a wider problem inside cells.
Kane cautioned that while the explanation is biologically plausible, it remains a working model. “A plausible mechanism is not the same as proof that this is what drives Alzheimer’s in patients,” he said.
Ageing May Play Role
The study also highlights a process called autophagy, which normally clears unwanted proteins from cells, including a-beta.
As this process becomes less efficient with age, autophagy may begin to accumulate inside neurons. This could increase the chances of it competing with tau and interfering with normal cell function.
What It Could Mean Going Forward
The findings may help explain why some earlier approaches to treatment have struggled to make a difference.
They also suggest that future research may look more closely at how these proteins interact inside cells, rather than focusing only on removing them once they have formed clumps.
Julian said the idea helps bring together different strands of research.
“This idea helps make sense of many results that previously seemed unrelated,” he said. “It gives us a clearer picture of what may be going wrong inside neurons and where new treatments might start.”
Kane said the study could point scientists toward new types of therapeutic strategies, but warned against overstating its immediacy.
“It could point researchers toward targets inside the neuron, such as protecting microtubules or preventing amyloid beta from interfering with tau—but I would not describe it as an immediate treatment breakthrough,” he said.
He added that the most important next step is confirming whether the process occurs in people.
“Researchers need to know when it happens, who it happens in, and whether it tracks with memory loss or functional decline over time,” he said.
Kane also urged caution in interpreting the findings.
“The most useful part of this study is that it moves the conversation from what we see after neurons are already damaged to what may be going wrong inside the neuron earlier,” he said. “That is where better treatments may eventually come from.”
Related Articles
Start your unlimited Newsweek trial
