Michael C. B. David, Magdalena A. Kolanko, Thomas D. Parker, Ramin Nilforooshan, Karl A. Zimmerman, Cristina Bonet Olivares, Karen Hoang, Johanna Brandt, Charikleia Triantafyllou, Peter J. Lally, Gregory Scott, CR&T Group of UKDRI, David J. Sharp, Paresh A. Malhotra
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LC and SN contrast, reflecting nucleus integrity, related to cognitive and neuropsychiatric symptoms, as well as cognitive decline and atrophy rates.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>LC – but not SN – integrity was reduced in AD versus controls (<i>b </i>= −0.39, <i>p</i> = 0.001) and within AD was associated with global cognition (<i>b </i>= 8.53, <i>p</i> = 0.04) and neuropsychiatric symptoms, accounting for SN. An AD subgroup with reduced SN integrity had worse cognition. LC integrity predicted plasma phosphorylated tau protein 217 (<i>b </i>= −0.30, <i>p</i> = 0.03). Lower LC and SN integrities were both related to faster cognitive decline (LC: <i>b </i>= −4.74, <i>p</i> = 0.048; SN: <i>b </i>= −2.27, <i>p</i> = 0.03), accounting for one another.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>Catecholaminergic nucleus integrity plays an important role in AD. Both systems are relevant to cognitive performance and decline. LC, in particular, relates closely to symptoms, pathology, and rate of progression.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>In symptomatic AD, LC integrity reflects cortical AD pathology, measured by pTau217.</li>\n \n <li>LC integrity predicts cognitive function in AD, independent of cortical atrophy.</li>\n \n <li>LC and SN integrity independently relate to attentional performance.</li>\n \n <li>Symptoms of anxiety, depression, and apathy are associated with lower LC integrity.</li>\n \n <li>LC and SN relate to cognitive decline rate and left LC predicts atrophy rate.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70749","citationCount":"0","resultStr":"{\"title\":\"Catecholaminergic nucleus integrity and Alzheimer's pathology, symptoms, and progression\",\"authors\":\"Michael C. 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引用次数: 0
摘要
去肾上腺素能蓝斑（LC）在阿尔茨海默病（AD）的早期病理积累，LC功能障碍有助于症状和疾病进展。我们研究了健康对照和AD参与者的LC和黑质（SN）完整性。方法93例AD患者和29例对照组行神经黑色素磁共振成像。LC和SN对比，反映了核的完整性，与认知和神经精神症状以及认知衰退和萎缩率有关。结果与对照组相比，AD患者的slc完整性降低（b = -0.39, p = 0.001），而AD患者的slc完整性与整体认知（b = 8.53, p = 0.04）和神经精神症状相关。神经网络完整性降低的AD亚组认知能力较差。LC完整性预测血浆磷酸化tau蛋白217 （b = -0.30, p = 0.03）。LC完整性和SN完整性越低，认知能力下降越快（LC: b = -4.74, p = 0.048; SN: b = -2.27, p = 0.03），相互抵消。儿茶酚胺能核完整性在AD中起重要作用。这两个系统都与认知能力的表现和衰退有关。LC尤其与症状、病理和进展速度密切相关。在症状性AD中，LC完整性反映皮层AD病理，通过pTau217测量。脑皮层完整性预测AD患者的认知功能，独立于皮质萎缩。LC和SN完整性分别与注意表现相关。焦虑、抑郁和冷漠症状与低LC完整性相关。左脑LC和左脑SN与认知衰退率有关，左脑LC预测脑萎缩率。
Catecholaminergic nucleus integrity and Alzheimer's pathology, symptoms, and progression
BACKGROUND
The noradrenergic locus coeruleus (LC) accumulates pathology early in Alzheimer's disease (AD), with LC dysfunction contributing to symptoms and disease progression. We investigated LC and substantia nigra (SN) integrity in healthy controls and AD participants.
METHODS
Ninety-three AD participants and 29 controls underwent neuromelanin magnetic resonance imaging. LC and SN contrast, reflecting nucleus integrity, related to cognitive and neuropsychiatric symptoms, as well as cognitive decline and atrophy rates.
RESULTS
LC – but not SN – integrity was reduced in AD versus controls (b = −0.39, p = 0.001) and within AD was associated with global cognition (b = 8.53, p = 0.04) and neuropsychiatric symptoms, accounting for SN. An AD subgroup with reduced SN integrity had worse cognition. LC integrity predicted plasma phosphorylated tau protein 217 (b = −0.30, p = 0.03). Lower LC and SN integrities were both related to faster cognitive decline (LC: b = −4.74, p = 0.048; SN: b = −2.27, p = 0.03), accounting for one another.
DISCUSSION
Catecholaminergic nucleus integrity plays an important role in AD. Both systems are relevant to cognitive performance and decline. LC, in particular, relates closely to symptoms, pathology, and rate of progression.
Highlights
In symptomatic AD, LC integrity reflects cortical AD pathology, measured by pTau217.
LC integrity predicts cognitive function in AD, independent of cortical atrophy.
LC and SN integrity independently relate to attentional performance.
Symptoms of anxiety, depression, and apathy are associated with lower LC integrity.
LC and SN relate to cognitive decline rate and left LC predicts atrophy rate.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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