Tang Chao, Yang Jiaxin, Lei Xiaoyang, Zhang Ming, Chen Yi, Peng Xiaoxue, He Dian
Department of Neurology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China.
Alzheimers Dement. 2025 Sep;21(9):e70605. doi: 10.1002/alz.70605.
Alzheimer's disease (AD) involves complex neurodegeneration in the locus coeruleus (LC) and substantia nigra (SN), critical brain regions affecting cognitive and emotional processes.
Using the National Alzheimer's Coordinating Center dataset of 11,583 participants, we conducted a multimodal analysis involving descriptive statistics, multifactorial regression, mediation analysis, and receiver operating characteristic curve assessment.
LC degenerative changes (18.57%) significantly exceeded SN changes (4.69%). The LC demonstrated stronger correlations with psychiatric symptoms and cognitive impairment. High LC/low SN damage patterns showed the strongest associations with mild cognitive impairment (OR = 2.38) and AD (OR = 3.56).
Our research reveals the heterogeneous degeneration patterns of LC and SN in AD, providing crucial insights into neurobiological mechanisms and potential strategies for early diagnosis and intervention.
This study provides a comprehensive framework for understanding the heterogeneous neurodegeneration patterns in AD through a detailed examination of the LC and SN. The research bridges the gap between neuroanatomical changes and neuropsychiatric symptoms, offering a more nuanced perspective on disease progression. Our findings challenge traditional linear models of neurodegeneration, emphasizing the complex and non-uniform nature of neural deterioration in AD. The study underscores the critical importance of investigating multiple neural nuclei to comprehensively understand neurodegenerative processes. By exploring the differential vulnerabilities of LC and SN, we provide new insights into potential targeted therapeutic interventions.
阿尔茨海默病（AD）涉及蓝斑（LC）和黑质（SN）的复杂神经退行性变，这两个脑区对认知和情感过程至关重要。
我们使用了包含11583名参与者的国家阿尔茨海默病协调中心数据集，进行了多模态分析，包括描述性统计、多因素回归、中介分析和受试者工作特征曲线评估。
LC的退行性变化（18.57%）显著超过SN的变化（4.69%）。LC与精神症状和认知障碍的相关性更强。高LC/低SN损伤模式与轻度认知障碍（OR = 2.38）和AD（OR = 3.56）的关联最为密切。
我们的研究揭示了AD中LC和SN的异质性退行性变模式，为神经生物学机制以及早期诊断和干预的潜在策略提供了关键见解。
本研究通过对LC和SN的详细检查，为理解AD中的异质性神经退行性变模式提供了一个全面的框架。该研究弥合了神经解剖学变化与神经精神症状之间的差距，为疾病进展提供了更细致入微的视角。我们的发现挑战了传统的神经退行性变线性模型，强调了AD中神经退化的复杂性和非均匀性。该研究强调了研究多个神经核以全面理解神经退行性过程的至关重要性。通过探索LC和SN的不同易损性，我们为潜在的靶向治疗干预提供了新的见解。
