Insights into neurodegeneration in Alzheimer’s disease from regional Aβ aggregation, iron level, and gene expression in postmortem human brain

Motivation: Quantifying Aβ in patients with Alzheimer's disease poses a challenge due to the colocalization of Aβ accumulation and iron deposition. Goal(s): Our goal was to simultaneously quantify Aβ and iron in ex-vivo human brains affected by AD. Approach: We used a novel subvoxel QSM method to measure Aβ and iron levels. The gene transcriptomic profiles were further investigated using PLS and ontological analysis. Results: Regions with higher diamagnetic and paramagnetic susceptibility were found higher levels of gene expression relating to the protein modification process and metal ion binding, as well as a relative abundance of exCA and glutamatergic neurons.Impact: The quantification of diamagnetic and paramagnetic susceptibility via APART-QSM can offer valuable insights into regional-specific vulnerabilities in Alzheimer’s disease, particularly those related to Aβ aggregation and iron accumulation. This can aid clinicians to better find therapeutic targets.