Brain structure changes appear seven years before Alzheimer’s plaques are detected
New research indicates that changes in the brain's outer layer can be detected at least seven years before amyloid plaques reach high levels. This challenges the traditional timeline of how Alzheimer's disease develops.
New research published in Nature Neuroscience reveals that subtle changes in the brain’s outer layer can be observed years before the accumulation of Alzheimer’s-associated amyloid-beta proteins is detected via brain scans. This study, led by James M. Roe and Yunpeng Wang from the University of Oslo, aimed to uncover if such cortical alterations manifest before amyloid buildup reaches a threshold detectable on scans.
The researchers analyzed data from three extensive, long-term studies of cognitive aging, focusing on cognitively healthy individuals without signs of dementia. Utilizing MRI scans to measure cerebral cortex thickness and PET scans to detect amyloid-beta plaques, the team divided participants into two groups: 77 individuals who later converted to high amyloid-beta levels and 412 who remained amyloid-negative.
By analyzing MRI data from one to ten years prior to each participant’s first positive amyloid scan, the researchers found that those who eventually developed high amyloid-beta displayed thicker cerebral cortexes and a slower rate of cortical thinning compared to their amyloid-negative counterparts. These structural differences were detectable at least seven years before amyloid levels reached a positive threshold and were particularly pronounced in the frontal regions of the brain.
Despite efforts to account for the effects of amyloid buildup in the statistical models, many of the cortical thickness differences persisted, suggesting these changes may be independent of early amyloid accumulation. The spatial pattern of cortical thickening aligned with the regions where amyloid-beta typically accumulates, and the timing of these structural changes mirrored the initial spread of amyloid plaques.
The study provides compelling evidence that the brain undergoes physical changes years before amyloid plaque formation is detectable, challenging the traditional view that amyloid plaques are the initial event in Alzheimer’s progression.
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