Cerebrospinal fluid YKL-40 relates to white matter hyperintensity progression in females but not males over a 6-year period.

IF 4 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2025-05-09 eCollection Date: 2025-04-01 DOI:10.1002/dad2.70110

Amalia J Peterson, Yunyi Sun, Derek B Archer, Hailey A Adegboye, Elizabeth E Moore, Isabella Deberghes, Kimberly R Pechman, Niranjana Shashikumar, W Hudson Robb, Abigail W Workmeister, T Bryan Jackson, Dandan Liu, Logan Dumitrescu, L Taylor Davis, Bennett A Landman, Kaj Blennow, Henrik Zetterberg, Timothy J Hohman, Angela L Jefferson

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引用次数: 0

Abstract

Introduction: Neuroinflammation may have sex-specific effects on white matter injury and impact the development of dementia.

Methods: Human chitinase-3-like protein-1 (YKL-40) concentrations at baseline were related to white matter hyperintensity (WMH) volume, free water (FW), and FW-corrected fractional anisotropy using linear effects models (for cross-sectional outcomes) and linear mixed-effects models (for longitudinal outcomes), adjusting for demographic and medical risk factors. Models were repeated with a sex-interaction term and then stratified by sex.

Results: In stratified analyses, greater baseline YKL-40 concentrations were associated with increased WMHs in females but not males in the parietal (females p = 0.04; males p = .34) and temporal lobes (females p = 0.005; males = p = 0.71) longitudinally. YKL-40 associations with FW and FW-corrected fractional anisotropy were null.

Discussion: Results suggest that neuroinflammation is a sex-specific driver of WMHs (but not FW) in females. Differential sequelae of neuroinflammation may be one reason that females have a greater burden of WMHs.

Highlights: ·Cerebrospinal fluid YKL-40 is associated with white matter hyperintensities in females but not males cross-sectionally and longitudinally.·Longitudinally, cerebrospinal fluid YKL-40 is associated with white matter hyperintensities in the parietal and temporal lobes, regions that exhibit early pathological changes in Alzheimer's disease .·Cerebrospinal fluid YKL-40 is not associated with white matter microstructural measures.

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脑脊液YKL-40与6年期间女性白质高强度进展有关，而与男性无关。

神经炎症可能对白质损伤有性别特异性影响，并影响痴呆的发展。方法：使用线性效应模型（用于横断面结果）和线性混合效应模型（用于纵向结果），调整人口统计学和医学危险因素，基线时人几丁质酶-3样蛋白-1 （YKL-40）浓度与白质高强度（WMH）体积、游离水（FW）和经FW校正的分数各向异性相关。用性别相互作用项重复模型，然后按性别分层。结果：在分层分析中，较高的基线YKL-40浓度与女性的WMHs升高有关，而与男性的WMHs升高无关(女性p = 0.04；男性p = 0.34)和颞叶(女性p = 0.005；男性= p = 0.71)纵向。YKL-40与FW和FW校正分数各向异性的关联为零。讨论：结果表明，神经炎症是女性WMHs（而不是FW）的性别特异性驱动因素。神经炎症的不同后遗症可能是女性wmh负担更大的原因之一。·脑脊液YKL-40在横切面和纵向上与女性白质高信号相关，而与男性无关。·纵向上，脑脊液YKL-40与在阿尔茨海默病中表现出早期病理改变的顶叶和颞叶白质高信号有关。·脑脊液YKL-40与白质微结构测量无关。

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.