The study suggests that the gold standard for imaging in Alzheimer's disease (amyloid-PET) has not been sensitive enough to detect early brain processes associated with the disease, such as the accumulation of amyloid plaques in the brain. The researchers found signs of Alzheimer's at least seven years before plaques become visible.
"We found that structural changes in the brain occur many years before high levels of plaque are seen on PET scans, which is the brain scan currently used to identify the earliest signs of Alzheimer's disease," says James Michael Roe.
He was a postdoctoral researcher at the Center for Lifespan Changes in Brain and Cognition (LCBC) at the Department of Psychology, University of Oslo at the time the study was conducted, and now works as International Scientific Lead at Cercare Medical. He was the main researcher on the study when he was working at LCBC.
May help with earlier detection
Roe emphasizes that the findings may mean that disease processes are already underway in the brain long before they become visible with today's most sensitive imaging tools.
"We found the earliest signal detected on brain scans to date, which could be useful for tracking the disease before symptoms emerge and may help with earlier detection," he says.
The researchers behind the study followed healthy individuals with regular brain scans (MRI) over nearly two decades. Using the imaging data, they were able to calculate precisely when - and in whom - plaques became detectable. They were then able to go back and examine MRI scans from the preceding decade, comparing brain changes in those who later developed plaques with those who did not.
"The most groundbreaking aspect of this study is that we found structural changes in the brain many years before the first signs of plaque buildup, which is considered to be the earliest sign of Alzheimer's disease," says Anders Martin Fjell, Professor at the Department of Psychology, and head of LCBC.
"These are cognitively well-functioning older individuals. What is unique here is that we have examined changes in brain structure in the years before the first scan revealed plaques," says Fjell.
Can be important to develop drugs that target processes other than amyloid plaque accumulation
He emphasizes that Alzheimer's disease is extremely difficult to treat, partly because it is so closely intertwined with ageing and is likely triggered by multiple factors.
"These findings suggest that there are brain changes that precede the first detectable signs of plaque accumulation, which is considered the earliest phase of the disease and occurs many years before cognitive symptoms start showing," he says.
Fjell clarifies that this either means:
1. That harmful processes either driving or resulting from plaque accumulation are already underway, despite plaques not being detectable by scanning,
or
2. That there are other processes giving rise to changes in the brain that occur even earlier than plaque accumulation.
"If the latter is true, it suggests it is important to continue developing drugs that target processes other than amyloid plaque accumulation. But we need more research on this," says Anders Martin Fjell.
Reference:
Roe, JM, Jagust, WJ, Landau, SM et al. (2026) Cortical thickness changes precede high levels of amyloid by at least 7 years. Nature Neuroscience. https://doi.org/10.1038/s41593-026-02363-4
