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

Yim, Younghee; Choi, Jong Duck; Cho, Jun Heong; Moon, Yeonsil; Han, Seol‐Heui; Moon, Won-Jin

doi:10.1007/s00234-021-02859-9

Cited by 6 publications

(8 citation statements)

References 47 publications

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“…We observed no significant correlations for other brain regions. This is consistent with the findings of Moon et al (2016) and Yim et al (2022) . However, Du et al (2018) reported a correlation between the left caudate nucleus and scale scores in the AD group.…”

Section: Discussionsupporting

confidence: 93%

“…Although the QSM values in some brain regions of APOE- ε 4 carriers were slightly increased compared with those of APOE- ε 4 non-carriers, no statistically significant differences were observed. This contradicts the results reported by Yim that APOE- ε 4 carry leads to elevated iron levels ( Yim et al, 2022 ) but is consistent with most of the findings reported by van Berge ( van Bergen et al, 2016 ). A reason for this discrepancy may be that in other studies, only one or a few slices of the ROI were selected, while we selected all consecutive slices of the ROI.…”

Section: Discussionsupporting

confidence: 73%

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Investigation of brain iron levels in Chinese patients with Alzheimer’s disease

Huang

Liu

et al. 2023

Front. Aging Neurosci.

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IntroductionWe aimed (i) to explore the diagnostic value of deep gray matter magnetic susceptibility in Alzheimer’s disease (AD) in China and (ii) to analyze its correlation with neuropsychiatric scales. Moreover, we conducted subgroup analysis based on the presence of the APOE-ε4 gene to improve the diagnosis of AD.MethodsFrom the prospective studies of the China Aging and Neurodegenerative Initiative (CANDI), a total of 93 subjects who could undergo complete quantitative magnetic susceptibility imaging and APOE-ε4 gene detection were selected. Differences in quantitative susceptibility mapping (QSM) values between and within groups, including AD patients, individuals with mild cognitive impairment (MCI), and healthy controls (HCs), both APOE-ε4 carriers and non-carriers, were analyzed.ResultsIn primary analysis, the magnetic susceptibility values of the bilateral caudate nucleus and right putamen in the AD group and of the right caudate nucleus in the MCI group were significantly higher than those in the HCs group (P < 0.05). In APOE-ε4 non-carriers, there were significant differences in more regions between the AD, MCI, and HCs groups, such as the left putamen and the right globus pallidus (P < 0.05). In subgroup analysis, the correlation between QSM values in some brain regions and neuropsychiatric scales was even stronger.DiscussionExploration of the correlation between deep gray matter iron levels and AD may provide insight into the pathogenesis of AD and facilitate early diagnosis in elderly Chinese. Further subgroup analysis based on the presence of the APOE-ε4 gene may further improve the diagnostic efficiency and sensitivity.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 73%

Investigation of brain iron levels in Chinese patients with Alzheimer’s disease

Huang

Liu

et al. 2023

Front. Aging Neurosci.

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“…Moreover, HIV infection was shown to increase apolipoprotein ε4 (ApoE4), an iron-upregulated biomolecule and AD risk factor, suggesting FIN involvement ( Ayton et al, 2015 ; Diouf et al, 2019 ; Kagerer et al, 2020 ). Furthermore, as viruses upregulate both ApoE4 and iron, they may be capable of triggering FIN directly ( Corder et al, 1998 ; Burt et al, 2008 ; Kuo et al, 2020 ; Gkouskou et al, 2021 ; Yim et al, 2022 ).…”

Section: Ferroptosis and The Endosomal-lysosomal Systemmentioning

confidence: 99%

Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration

et al. 2022

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Graphical AbstractBoth HIV-1 and cART alter the lysosomes, increasing intracellular iron and the risk of ferroptosis. Dysfunctional lysosomes release the ferroptosis drivers iron, Ca2+ and cathepsin B (catB), promoting neuronal and oligodendrocyte loss, reflected in the white and gray matter pathology. The host responds to lysosomal damage by activating an epigenetic axis comprised of bromodomain 4 (BRD4) and microRNA-29 family (miR-29) that promptly suppresses lysosomal function, lowering ferritinophagy. As there is an inverse relationship between miR-29 and BRD4, HIV-1 inhibition of miR-29, upregulates BRD4, blocking ferritinophagy. The BRD4/miR-29 system also inhibits iron regulatory protein-2 (IRP-2) and augments cystine/glutamate antiporter xCT (SLC7A11), lowering the odds of ferroptosis.

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“…Previous studies have shown significant volume loss in the hippocampus and amygdala in homozygous ε4 carriers with AD compared with noncarriers (Filippini et al, 2009;Liu et al, 2010;Tanaka et al, 1998). However, few studies have been performed to evaluate the prediction of an ApoE ε4 carrier with images (Honea et al, 2009;Kim et al, 2013;Yim et al, 2022).…”

Section: Ta B L Ementioning

confidence: 99%

“…This technique could be used to predict ApoE ε4 status with GMV and demographic parameters related to cognitive function. Few studies have evaluated the prediction of ApoE ε4 status with both GMV and demographic parameters such as age and the mini–mental state examination (MMSE) score (Honea et al., 2009 ; Kim et al., 2013 ; Yim et al., 2022 ). ApoE ε4 carriers are thought to show a close relationship between decreased cognitive function and brain atrophy, regardless of whether they are AD patients or not.…”

Section: Introductionmentioning

confidence: 99%

Predicting the apolipoprotein E ε4 allele carrier status based on gray matter volumes and cognitive function

Kim,

Tian,

Jung

et al. 2024

Brain and Behavior

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BackgroundApolipoprotein E (ApoE) ε4 carriers have a higher risk of developing Alzheimer's disease (AD) and show brain atrophy and cognitive decline even before diagnosis.ObjectiveTo predict ApoE ε4 status using gray matter volume (GMV) obtained from magnetic resonance imaging images and demographic data with machine learning (ML) methods.MethodsWe recruited 74 participants (25 probable AD, 24 amnestic mild cognitive impairment, and 25 cognitively normal older people) with known ApoE genotype (22 ApoE ε4 carriers and 52 noncarriers) and scanned them with three‐dimensional (3D) T1‐weighted (T1W) and 3D double inversion recovery (DIR) sequences. We extracted GMV from regions of interest related to AD pathology and used them as features along with age and mini–mental state examination (MMSE) scores to train different ML models. We performed both receiver operating characteristic curve analysis and the prediction analysis of the ApoE ε4 carrier with different ML models.ResultsThe best model of ML analyses was a cubic support vector machine (SVM3) that used age, the MMSE score, and DIR GMVs at the amygdala, hippocampus, and precuneus as features (AUC = .88). This model outperformed models using T1W GMV or demographic data alone.ConclusionOur results suggest that brain atrophy with DIR GMV and cognitive decline with aging can be useful biomarkers for predicting ApoE ε4 status and identifying individuals at risk of AD progression.

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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

Cited by 6 publications

References 47 publications

Investigation of brain iron levels in Chinese patients with Alzheimer’s disease

Investigation of brain iron levels in Chinese patients with Alzheimer’s disease

Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration

Predicting the apolipoprotein E ε4 allele carrier status based on gray matter volumes and cognitive function

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