Alzheimer's research has long centered on gray matter, where neurons' cell bodies sit and where the disease's signature lesions pile up. A study led by the Neuroimaging of Aging and Neurodegenerative Diseases group at the Sant Pau Research Institute (IR Sant Pau), published in Alzheimer's & Dementia, adds weight to a different view: the brain's white matter, the wiring that connects those neurons, is already changing early in the disease process.
The team used a diffusion MRI metric known as PSMD, short for peak width of skeletonized mean diffusivity. It is designed to capture microscopic alterations in white matter tracts that conventional MRI scans miss. In both sporadic Alzheimer's disease and Alzheimer's disease linked to Down syndrome, PSMD flagged white matter abnormalities at an early stage.
The timing in the Down syndrome group is what stands out. Those changes showed up at roughly age 38, about 15 years before dementia symptoms usually become clinically obvious in this population. People with Down syndrome carry a genetically driven, highly predictable risk of Alzheimer's, which makes them an informative group for studying how the disease unfolds before symptoms appear - and a measure that registers change that far ahead could help identify who might benefit from early intervention or be enrolled in prevention trials.
The broader message from the researchers is that Alzheimer's is not a gray matter disease alone. White matter is altered early and carries useful information about how the disease progresses, which argues for including measures like PSMD alongside the amyloid and tau markers that currently dominate diagnostic work.