CSF biomarkers are differentially linked to brain areas high and low in noradrenaline, dopamine and serotonin across the Alzheimer's disease spectrum.

IF 4.1 Q1 CLINICAL NEUROLOGY
Brain communications Pub Date : 2025-01-23 eCollection Date: 2025-01-01 DOI:10.1093/braincomms/fcaf031
Lena Haag, Elisa Lancini, Renat Yakupov, Gabriel Ziegler, Yeo-Jin Yi, Falk Lüsebrink, Wenzel Glanz, Oliver Peters, Eike Jakob Spruth, Slawek Altenstein, Josef Priller, Luisa Sophie Schneider, Xiao Wang, Lukas Preis, Frederic Brosseron, Nina Roy-Kluth, Klaus Fliessbach, Michael Wagner, Steffen Wolfsgruber, Luca Kleineidam, Alfredo Ramirez, Annika Spottke, Frank Jessen, Jens Wiltfang, Anja Schneider, Niels Hansen, Ayda Rostamzadeh, Katharina Buerger, Michael Ewers, Robert Perneczky, Daniel Janowitz, Boris-Stephan Rauchmann, Stefan Teipel, Ingo Kilimann, Doreen Goerss, Christoph Laske, Matthias H Munk, Michael Heneka, Peter Dechent, Stefan Hetzer, Klaus Scheffler, Emrah Düzel, Matthew J Betts, Dorothea Hämmerer
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引用次数: 0

Abstract

Neurotransmitter systems of noradrenaline, dopamine, serotonin and acetylcholine are implicated in cognitive functions such as memory, learning and attention and are known to be altered in neurodegenerative diseases like Alzheimer's disease. Specific brain structures involved in these systems, e.g. the locus coeruleus, the main source of noradrenaline in the cortex, are in fact affected earliest by Alzheimer's disease tau pathology. Preserved volumetric neurotransmitter specific brain areas could therefore be an important neural resource for cognitive reserve in aging. The aim of this study was to determine whether volumes of brain areas known to be high in neurotransmitter receptors are relatively preserved in individuals with lower levels of Alzheimer's disease pathology. Based on the Human Protein Atlas for neurotransmitter receptor distribution, we distinguished between 'areas high and low' in noradrenaline, dopamine, serotonin and acetylcholine and assessed associations of atrophy in those areas with CSF amyloid-ß 42/40, CSF phosphorylated tau protein and cognitive function across healthy controls (n = 122), individuals with subjective cognitive decline (n = 156), mild cognitive impairment or mild Alzheimer's disease dementia (n = 126) using structural equation modelling. CSF pathology markers were inversely correlated and showed a stronger association with disease severity, suggesting distinguishable interrelatedness of these biomarkers depending on the stage of Alzheimer's disease dementia. Across groups, amyloid pathology was linked to atrophy in areas high as well as low in neurotransmitter receptor densities, while tau pathology did not show any significant link to brain area volumes for any of the neurotransmitters. Within disease severity groups, individuals with more amyloid pathology showed more atrophy only in 'areas high in noradrenaline', whereas for dopamine tau pathology was linked to higher volumes in areas low in receptor density possibly indicating compensatory mechanisms. Furthermore, individuals with more tau pathology showed a selective decrease in memory function while amyloid pathology was related to a decline in executive function and language capacity as well as memory function. In summary, our analyses highlight the benefits of investigating disease-relevant factors in Alzheimer's disease using a multivariate multigroup approach. Assessing multivariate dependencies in different disease stages and across individuals revealed selective links of pathologies, cognitive decline and atrophy in particular for areas modulated by noradrenaline, dopamine and serotonin.

在整个阿尔茨海默病谱系中,脑脊液生物标志物与去甲肾上腺素、多巴胺和血清素含量高和低的大脑区域有不同的联系。
去甲肾上腺素、多巴胺、血清素和乙酰胆碱等神经递质系统与记忆、学习和注意力等认知功能有关,已知在阿尔茨海默病等神经退行性疾病中会发生改变。参与这些系统的特定大脑结构,例如蓝斑,皮质中去甲肾上腺素的主要来源,实际上最早受到阿尔茨海默病tau病理学的影响。因此,保留的体积神经递质特异性脑区可能是衰老认知储备的重要神经资源。这项研究的目的是确定在阿尔茨海默病病理水平较低的个体中,已知的神经递质受体高的大脑区域的体积是否相对保存。基于神经递质受体分布的人类蛋白质图谱,我们区分了去甲肾上腺素、多巴胺、血清素和乙酰胆碱的“高和低区域”,并评估了健康对照组(n = 122)、主观认知能力下降个体(n = 156)、脑脊液淀粉样蛋白- β 42/40、脑脊液磷酸化tau蛋白和认知功能区域萎缩的相关性。轻度认知障碍或轻度阿尔茨海默病痴呆(n = 126)使用结构方程模型。脑脊液病理标志物呈负相关,且与疾病严重程度有更强的相关性,这表明这些生物标志物在阿尔茨海默病痴呆的分期上存在可区分的相互关系。在各组中,淀粉样蛋白病理与神经递质受体密度高和低的区域的萎缩有关,而tau病理与任何神经递质的大脑面积没有任何显著联系。在疾病严重程度组中,具有更多淀粉样蛋白病理的个体仅在“去甲肾上腺素高的区域”表现出更多的萎缩,而多巴胺tau病理与低受体密度区域的高容量有关,这可能表明代偿机制。此外,tau蛋白病理更多的个体表现出记忆功能的选择性下降,而淀粉样蛋白病理与执行功能、语言能力以及记忆功能的下降有关。总之,我们的分析强调了使用多变量多组方法研究阿尔茨海默病疾病相关因素的益处。评估不同疾病阶段和个体之间的多变量依赖关系揭示了病理、认知衰退和萎缩的选择性联系,特别是在去甲肾上腺素、多巴胺和血清素调节的区域。
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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