Recent research indicates that brain alterations associated with Alzheimer’s disease may begin over seven years before detection by current imaging methods. Traditionally, the appearance of amyloid plaques on amyloid-PET scans has been the earliest sign of Alzheimer’s disease. However, new findings suggest structural changes appear on MRI scans long before plaques, indicating an earlier start of the disease process.
The study involved cognitively healthy older adults without memory or thinking issues who underwent repeated MRI scans over two decades. Some participants developed amyloid plaques, while others did not. Researchers pinpointed when plaques first appeared on PET scans, then reviewed MRI scans from the previous decade. They discovered structural brain changes in those who later developed plaques at least seven years prior to visible plaque detection.
Published in Nature Neuroscience, these findings challenge current definitions of Alzheimer’s onset. If disease activity precedes plaque appearance on scans, existing methods might overlook significant parts of the disease timeline.
Researchers suggest two possible explanations: Alzheimer’s-related biological processes might affect the brain before plaques are detectable, possibly contributing to their formation or accompanying early plaque changes invisible to current imaging. Alternatively, distinct mechanisms might cause changes before amyloid accumulation.
Dr. Lucy Hooper, a GP and Coyne Medical co-founder, suggests these insights could revise thoughts on intervention timing. “This prolonged development period means there’s more opportunity to prevent or delay Alzheimer’s,” she mentioned to Newsweek. Previous studies already indicate changes in cerebrospinal fluid and blood are detectible decades before amyloid appears on scans.
According to Hooper, soluble amyloid forms might harm brain connections before plaques are apparent. Factors such as inflammation, immune cell changes, blood vessel alterations, and brain glymphatic system disruptions might occur independent of plaques. These findings could guide future advancements in diagnosis and treatment.
“A deeper understanding of biology enhances diagnosis and prevention,” Hooper stated. While plasma p-tau217 blood testing is used in clinical settings for Alzheimer’s diagnosis, it isn’t flawless due to possible false results. Better biological markers could help develop therapies to reduce or prevent Alzheimer’s. Though many treatments focus on amyloid, researchers are increasingly considering inflammation, metabolic changes, and the glymphatic system.
Reference: James M. Roe, et al. Cortical thickness changes precede high levels of amyloid by at least 7 years. Nature Neuroscience, 2026; DOI: 10.1038/s41593-026-02363-4
Inquiries on this story can be directed to Newsweek editors: Kara Dolman and Gray R. Thomas.
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