Alzheimer’s disease may begin changing the brain years earlier than doctors have been able to see with standard scans.
A new study from the University of Oslo found changes in brain structure at least seven years before the buildup of amyloid plaques became visible on a commonly used type of brain scan.
The finding could change how scientists think about the earliest stages of the disease.
Alzheimer’s is the most common cause of dementia. It slowly damages memory, thinking and the ability to manage everyday life, but the biological changes behind the disease are believed to begin long before obvious symptoms appear.
Finding those early changes is one of the biggest goals in Alzheimer’s research.
One important sign is the buildup of a substance called amyloid in the brain. Amyloid can collect into plaques between brain cells, and these plaques are strongly linked to Alzheimer’s disease. Special scans called amyloid PET scans can show when enough amyloid has accumulated to become detectable.
Because amyloid can appear years before memory problems, PET imaging has become an important tool for studying early Alzheimer’s. However, the new research suggests that even these sensitive scans may be seeing the disease story after other changes have already begun. The brain may be changing while amyloid PET results still appear negative.
The study was led by researchers at the Department of Psychology at the University of Oslo. James Michael Roe was the main researcher while working at the university’s Center for Lifespan Changes in Brain and Cognition. The findings were published in the journal Nature Neuroscience.
The researchers had access to something especially valuable: repeated brain scans collected from healthy adults over nearly 20 years. Instead of looking at people only after amyloid plaques were already present, the team could go back through years of earlier scans. This allowed them to study what happened before amyloid became detectable.
The participants were older adults who were still functioning well mentally. Researchers used repeated PET scans to estimate when each person first developed detectable amyloid plaques. They then examined MRI scans from the previous decade and compared people who later developed plaques with people who did not.
MRI and PET scans provide different kinds of information. PET can be designed to look for particular substances such as amyloid, while MRI gives detailed pictures of the brain’s structure. By combining information from both, the researchers could ask whether physical changes in the brain came before visible amyloid buildup.
They found that structural brain changes could be detected many years before amyloid PET scans became positive. According to the researchers, the signal appeared at least seven years before plaques were visible. Roe described it as the earliest brain-scan signal detected so far in relation to the later appearance of Alzheimer’s-related amyloid.
The result does not mean that doctors can now diagnose Alzheimer’s seven years earlier with an ordinary MRI scan. The changes were found by carefully analyzing repeated scans from groups of people over many years. More work is needed before researchers know whether the same approach can accurately identify disease in an individual patient.
Still, the finding raises an important question about what is happening during this previously hidden period. One possibility is that harmful changes connected to amyloid are already occurring even though there is not yet enough amyloid for PET scans to detect. In that case, amyloid may still be involved from a very early stage.
Another possibility is more challenging to current ideas. Changes unrelated to amyloid buildup may begin first and could help create the conditions that later lead to plaques. If this is true, Alzheimer’s may have important early drivers that current amyloid-focused tests do not directly measure.
Professor Anders Martin Fjell, head of the Oslo research center, said Alzheimer’s is difficult to treat partly because it is closely connected with aging and probably involves several biological processes.
The new findings could therefore support continued research into treatments that target more than amyloid alone. Scientists are already investigating inflammation, blood vessels, abnormal tau, metabolism and other possible contributors to brain decline.
Earlier detection could also matter because Alzheimer’s treatments are generally expected to work best before extensive brain damage has occurred. Once large numbers of brain cells have been lost, restoring normal function becomes much harder. Finding reliable warning signs years before symptoms could eventually give doctors a larger window in which to intervene.
The study has several strengths. Following healthy people for nearly two decades allowed the researchers to look backward from the moment amyloid became detectable instead of simply comparing younger and older patients at one point in time. That makes the timing of the observed brain changes particularly interesting.
However, the results should not be treated as a new clinical test. Brain structure naturally changes with age, and many older people never develop Alzheimer’s dementia. Researchers will need to show that the early MRI patterns can reliably distinguish future Alzheimer’s disease from ordinary aging and from other brain conditions.
The study also cannot yet prove what causes the early structural changes. They might be part of the process that leads to amyloid buildup, a response to very small amounts of amyloid that PET cannot yet see, or a separate process occurring alongside it. Answering that question will require additional studies using different biological markers and larger groups of people.
Even with these uncertainties, the work pushes the Alzheimer’s timeline further back. It suggests that the period before visible amyloid plaques may not be biologically quiet at all. Understanding what happens during those hidden years could eventually lead to earlier detection and new ways of slowing the disease before memory begins to fail.
