Galgani Alessandro, Lombardo Francesco, Frijia Francesca, Scotto Marco, Tognoni Gloria, Pavese Nicola, Giorgi Filippo Sean
Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, Pisa, Italy.
Department of Radiology, Fondazione Toscana "G. Monasterio", Pisa, Italy.
Neurodegener Dis. 2025;25(2):53-66. doi: 10.1159/000544882. Epub 2025 Mar 3.
Experimental data suggest sexual dimorphism in the Locus Coeruleus (LC), with females exhibiting higher neuronal count and noradrenergic activity. In Alzheimer's disease (AD), progressive LC dysfunction may contribute early to pathogenesis, and female sex is a key risk factor for AD. This study aimed to investigate if such sex differences exist in humans and whether they influence the relationship between LC degeneration and AD features, such as cortical atrophy and cognitive decline.
Fifty-three healthy controls (HCs), 70 mild cognitive impaired (MCI) participants, and 29 Alzheimer's disease demented (ADD) patients underwent high-field brain MRI with LC-sensitive sequences following detailed neuropsychological and neurological assessments. LC integrity was measured using the LC contrast ratio (LCCR) parameter based on a previously published template approach.
Within the HC and MCI groups, females showed higher LCCR values than males. A significant sex effect was observed in the relationship between LC integrity and cortical volume in the frontotemporal cortices, with males showing a stronger association.
LC structure and function may differ between sexes, influencing AD pathophysiology through distinct mechanisms. While this sexual dimorphism may have a minor role, it should be considered in clinical investigations and drug development research.
实验数据表明蓝斑（LC）存在性别差异，女性表现出更高的神经元数量和去甲肾上腺素能活性。在阿尔茨海默病（AD）中，LC功能的进行性障碍可能在疾病早期就对发病机制产生影响，而女性是AD的一个关键风险因素。本研究旨在调查人类是否存在这种性别差异，以及它们是否会影响LC变性与AD特征（如皮质萎缩和认知衰退）之间的关系。
53名健康对照者（HCs）、70名轻度认知障碍（MCI）参与者和29名阿尔茨海默病痴呆（ADD）患者在经过详细的神经心理学和神经学评估后，接受了采用LC敏感序列的高场脑MRI检查。基于先前发表的模板方法，使用LC对比率（LCCR）参数测量LC完整性。
在HC组和MCI组中，女性的LCCR值高于男性。在额颞叶皮质的LC完整性与皮质体积之间的关系中观察到显著的性别效应，男性表现出更强的相关性。
LC的结构和功能可能因性别而异，通过不同机制影响AD的病理生理学。虽然这种性别差异可能作用较小，但在临床研究和药物研发中应予以考虑。
