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Magnetic susceptibility in the deep gray matter may be modulated by apolipoprotein E4 and age with regional predilections: a quantitative susceptibility mapping study

  • Diagnostic Neuroradiology
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Abstract

Purpose

To examine the relationship between apolipoprotein E gene (APOE) mutation status and iron accumulation in the deep gray matter of subjects with cognitive symptoms using quantitative susceptibility mapping (QSM).

Methods

A total of 105 patients with cognitive symptoms were enrolled. QSM data were generated from 3D gradient-echo data using an STI Suite algorithm. A region of interest-based analysis with QSM was performed in the deep gray matter. Differences between APOE4 carriers and non-carriers were assessed by analysis of covariance. Multiple regression analysis was performed to identify the factors associated with magnetic susceptibility.

Results

Clinical characters such as age, education, MMSE, vascular risk burden, and systolic blood pressure differ between APOE4 carrier and non-carrier groups. The APOE4 carrier group had higher magnetic susceptibility values than the non-carrier group, with significant differences in the caudate (p = 0.004), putamen (p < 0.0001), and globus pallidus (p < 0.0001) which imply higher iron accumulation. In a multiple regression analysis, APOE4 status was found to be a predictor of magnetic susceptibility value in the globus pallidus (p = 0.03); age for magnetic susceptibility value in the caudate nucleus (p = 0.0064); and age and hippocampal atrophy for magnetic susceptibility value in the putamen (p < 0.05).

Conclusion

Our study demonstrates that magnetic susceptibility in globus pallidus is related to APOE4 status while those of caudate and putamen are related to other factors including age. It suggests that brain iron accumulation in the deep gray matter is modulated by APOE4 and age with differential regional predilection.

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Data availability

Due to the nature of this research, participants of this study did not agree for their data to be shared publicly, so supporting data is not available.

Code availability

Code sharing is not applicable to this article as no codes were generated during the current study.

Abbreviations

AD:

Alzheimer’s disease

CSF:

Cerebrospinal fluid

MCI:

Mild cognitive impairment

SCI:

Subjective cognitive impairment

EOAD:

Early-onset Alzheimer’s disease

MRI:

Magnetic resonance imaging

QSM:

Quantitative susceptibility mapping

APOE :

Apolipoprotein E gene

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Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. 2017R1A2B4010634) and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No. HI18C1038).

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Authors and Affiliations

  1. Department of Radiology, Konkuk University Medical Center, Konkuk University School of Medicine, 120-1, Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul, 05030, Republic of Korea

    Younghee Yim, Jong Duck Choi, Jun Heong Cho & Won-Jin Moon

  2. Department of Radiology, Chung-Ang University, College of Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea

    Younghee Yim

  3. Department of Neurology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea

    Yeonsil Moon & Seol-Heui Han

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  1. Younghee Yim
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  2. Jong Duck Choi
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  3. Jun Heong Cho
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  4. Yeonsil Moon
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Contributions

Y. Yim and W. Moon took full responsibility for the conception and design of the study, the collection, analysis, and interpretation of the data, and the drafting of the manuscript. JD Choi and J. H. Cho were in charge of data collection and analysis. Y. Moon and S. H. Han helped with the design of the study and critical revision of the manuscript for important intellectual content. Y. Moon and S. H. Han were in charge of data collection and helped study design. All authors approved the final version of the manuscript to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Won-Jin Moon.

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Yim, Y., Choi, J.D., Cho, J.H. et al. Magnetic susceptibility in the deep gray matter may be modulated by apolipoprotein E4 and age with regional predilections: a quantitative susceptibility mapping study. Neuroradiology 64, 1331–1342 (2022). https://doi.org/10.1007/s00234-021-02859-9

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