The effect of beta-amyloid and tau protein aggregations on magnetic susceptibility of anterior hippocampal laminae in Alzheimer's diseases

Previous studies have reported the changes of magnetic susceptibility induced by iron deposition in hippocampus of Alzheimer's disease (AD) brains. It is well-known that hippocampus is divided into well-defined laminar architecture, which, however, is difficult to be resolved with in-vivo MRI due to the limited imaging resolution. The present study aims to investigate layer-specific magnetic susceptibility in the hippocampus of AD patients using high-resolution ex-vivo MRI, and elucidate its relationship with beta amyloid (Aβ) and tau protein histology. We performed quantitative susceptibility mapping (QSM) and T2* mapping on postmortem anterior hippocampus samples from four AD, four Primary Age-Related Tauopathy (PART), and three control brains. We manually segmented each sample into seven layers, including four layers in the cornu ammonis1 (CA1) and three layers in the dentate gyrus (DG), and then evaluated AD-related alterations of susceptibility and T2* values and their correlations with Aβ and tau in each hippocampal layer. Specifically, we found (1) layer-specific variations of susceptibility and T2* measurements in all samples; (2) the heterogeneity of susceptibility were higher in all layers of AD patients compared with the age- and gender-matched PART cases while the heterogeneity of T2* values were lower in four layers of CA1; and (3) voxel-wise MRI-histological correlation revealed both susceptibility and T2* values in the stratum molecular (SM) and stratum lacunosum (SL) layers were correlated with the Aβ content in AD, while the T2* values in the stratum radiatum (SR) layer were correlated with the tau content in the PART but not AD. These findings suggest a selective effect of the Aβ- and tau-pathology on the susceptibility and T2* values in the different layers of anterior hippocampus. Particularly, the alterations of magnetic susceptibility in the SM and SL layers may be associated with Aβ aggregation, while those in the SR layermay reflect the age-related tau protein aggregation.