Histologically validated diffusion MRI signatures of neuroinflammation and neurodegeneration in Alzheimer disease

Researchers developed a new MRI method called generalized diffusion basis spectrum imaging (g-DBSI) that decomposes brain tissue signals into biologically interpretable components. In postmortem brains of Alzheimer disease patients, certain g-DBSI parameters (RIF and RAF) were able to map cell density and neurofilament density, with their ratio (RIF/RAF) more accurately tracking inflammatory cell density and amyloid-beta around plaques. In 112 living patients stratified by amyloid levels, g-DBSI metrics changed depending on amyloid burden: in low-amyloid individuals, RIF and RAF increased together with amyloid, indicating early neuroinflammatory development, while in high-amyloid individuals, RIF/RAF increased and RAF declined, indicating established neuroinflammatory remodeling and neurofilament loss. This method could serve as a clinically applicable biomarker of neuroinflammation and neurodegeneration in Alzheimer disease.