Quantitative susceptibility mapping of the brain is associated with inflammatory changes in Alzheimer’s disease related areas

Accumulation of paramagnetic substances in brain tissue may constitute a feature of Alzheimer's disease (AD) associated with inflammatory processes. This study employed MRI quantitative susceptibility mapping (QSM), as an index of paramagnetic load, to assess its association with brain Aβ and tau aggregates, as well as inflammatory biomarkers. We assessed QSM and T1-weighted MRI scans from 315 participants in the TRIAD cohort, including young-controls and individuals across the AD spectrum. Imaging was performed at baseline, with follow-up assessments at 12 and 24 months. Mean-cortical and subcortical susceptibility values were measured, and correlations with AD-relevant plasma and CSF inflammatory biomarkers. At baseline, AD patients had significantly greater QSM than age-matched controls in the posterior cingulate cortex, precuneus, and basal ganglia. After 24 months, QSM increased in the anterior cingulate in MCI, while dementia cases showed increase in the pallidum and hippocampus. Multiple comparison analysis indicated correlation between QSM and immune biomarkers IL-10RB, PD-L1, SCF, TWEAK, CSF-1, CXCL9, HGF, and CD40, but not with brain Aβ or tau-related biomarkers. Our findings reveal that the magnitude of tissue susceptibility load, as measured by QSM, reflects tissue inflammation rather than protein aggregation. QSM provides new insights into tissue dysfunction, with potential applications in AD therapeutic development.