Associations between APOE-TOMM40 '523 haplotypes and limbic system white matter microstructure.

IF 4 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2025-04-06 eCollection Date: 2025-04-01 DOI:10.1002/dad2.70099

Katelyn E Mooney, Derek B Archer, Aditi Sathe, Timothy J Hohman, Ose Kadiri, Melissa Lamar, Konstantinos Arfanakis, Lei Yu, Lisa L Barnes, Kacie D Deters

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引用次数: 0

Abstract

Introduction: We assessed associations between apolipoprotein E Translocase of Outer Mitochondrial Membrane 40 (APOE-TOMM40)-'523 haplotypes and white matter microstructure (WMM) across limbic tracts important for memory and cognition in non-Hispanic Black and White individuals.

Methods: Linear regression models, stratified by APOE and racialized groups, assessed associations between TOMM40-'523-S and limbic tract WMM free-water (FW) and free-water-corrected fractional anisotropy (FAFWcorr).

Results: Black-ε4+-one-'523-S carriers had lower FW in the cingulum and inferior longitudinal fasciculus compared to Black-ε4+-no-'523-S carriers. Additionally, Black-ε4+-one-'523-S carriers had lower FW in the cingulum, uncinate, and fornix, and higher FA_FWcorr in the uncinate compared to Black-ε4+-'523-S/S carriers. White-ε3/ε3-'523-S/S carriers had lower FAFWcorr in the cingulum and inferior temporal gyrus compared to White-ε3/ε3-no-'523-S carriers, and lower FAFWcorr in the cingulum compared to White-ε3/ε3-one-'523-S carriers.

Discussion: This supports prior work that '523-S is associated with abnormal aging in White-ε3/ε3 carriers, but is potentially risk-mitigating in Black-ε4+ carriers, while suggesting a differential effect by racialized background of APOE on WMM.

Highlights: White matter microstructure (WMM) across limbic tracts important for cognition was measured by diffusion MRI.Black apolipoprotein E (APOE) ε4+ carriers with one copy of TOMM40-'523-S had normal aging WMM metrics across several tracts, including the cingulum bundle, uncinate fasciculus, fornix, and inferior longitudinal fasciculus.White APOE ε3/ε3 carriers with two copies of TOMM40-'523-S had abnormal aging WMM metrics in the cingulum bundle and inferior temporal gyrus.APOE associations with aging may differ in racialized groups due to TOMM40-'523-S copy number.

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APOE-TOMM40 '523单倍型与大脑边缘系统白质微观结构的关系

简介：我们评估了非西班牙裔黑人和白人的载脂蛋白E转位酶外线粒体膜40 (APOE-TOMM40)-'523单倍型与大脑边缘束白质微观结构（WMM）之间的关系，这些白质微观结构对记忆和认知很重要。方法：采用线性回归模型，按APOE和种族化组分层，评估TOMM40- 523-S与边缘束WMM - free-water （FW）和free-water-corrected分数各向异性（FAFWcorr）之间的关系。结果：黑色-ε4+- 1 -'523-S携带者与黑色-ε4+- 1 -'523-S携带者相比，扣带和下纵束FW较低。此外，与黑色-ε4+- 1 - 523-S/S携带者相比，黑色-ε4+- 1 - 523-S携带者在扣带、钩侧和穹窿处的FW较低，钩侧的FAFWcorr较高。White-ε3/ε3-'523-S/S携带者的扣带和颞下回FAFWcorr低于White-ε3/ε3-'523-S携带者，扣带FAFWcorr低于White-ε3/ε3- 1 -'523-S携带者。讨论：这支持了先前的研究，即'523-S与白色-ε3/ε3携带者的异常衰老有关，但在黑色-ε4+携带者中可能降低风险，同时提示APOE种族化背景对WMM的差异影响。重点：应用弥散磁共振成像（diffusion MRI）测量脑边缘束白质微结构（WMM）。携带1个TOMM40- 523-S拷贝的黑色载脂蛋白E (APOE) ε4+在包括扣带束、钩状束、穹窿和下纵束在内的多个束上的衰老WMM指标正常。携带2个TOMM40- 523-S基因的白色APOE ε3/ε3携带者在扣带束和颞下回出现异常的老龄WMM指标。由于TOMM40- 523-S拷贝数不同，APOE与衰老的关联可能在种族化群体中有所不同。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Medicine-Psychiatry and Mental Health

CiteScore

7.80

自引率

7.50%

发文量

101

审稿时长

8 weeks

期刊介绍： Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.