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

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-01-29 DOI:10.1002/alz.14459

Aocai Yang, Jixin Luan, Manxi Xu, Lei Du, Kuan Lv, Pianpian Hu, Ni Shu, Zhen Yuan, Amir Shmuel, Guolin Ma

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Abstract

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.

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.