Regional brain iron correlates with transcriptional and cellular signatures in Alzheimer's disease.

INTRODUCTION

The link between overload brain iron and transcriptional/cellular signatures in Alzheimer's disease (AD) remains inconclusive.

METHODS

Iron deposition in 41 cortical and subcortical regions of 30 AD patients and 26 healthy controls (HCs) was measured using quantitative susceptibility mapping (QSM). The expression of 15,633 genes was estimated in the same regions using transcriptomic data from the Allen Human Brain Atlas (AHBA). Partial least square (PLS) regression was used to identify the association between the healthy brain gene transcription and aberrant regional QSM signal in AD. The biological processes and cell types associated with the linked genes were evaluated.

RESULTS

Gene ontological analyses showed that the first PLS component (PLS1) genes were enriched for biological processes relating to the "protein phosphorylation" and "metal ion transport". Additionally, these genes were expressed in microglia (MG) and glutamatergic neurons (GLUs).

DISCUSSION

Our findings provide mechanistic insights from transcriptional and cellular signatures into regional iron accumulation measured by QSM in AD.

HIGHLIGHTS

Spatial patterns of iron deposition changes in AD correlate with cortical spatial expression genes in healthy subjects. The identified gene transcription profile underlies aberrant iron accumulation in AD was enriched for biological processes relating to "protein phosphorylation" and "metal ion transport". The related genes were predominantly expressed in MG and GLUs.