Gabriel Vincent, Bousiges Olivier, Mondino Mary, Cretin Benjamin, Philippi Nathalie, Muller Candice, Anthony Pierre, Demuynck Catherine, de Sousa Paulo Loureiro, Botzung Anne, Sanna Léa, Chabran Eléna, Blanc Frédéric
ICube Laboratory UMR-7357 and FMTS (Fédération de Médecine Translationnelle de Strasbourg), IMIS Team and IRIS Platform, University of Strasbourg and CNRS, Strasbourg, France.
Laboratory of Biochemistry and Molecular Biology, University Hospital of Strasbourg, Strasbourg, France.
Geroscience. 2025 Jan 17. doi: 10.1007/s11357-025-01513-z.
The differential mechanisms between proteinopathies and neurodegeneration in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) remain unclear. To address this issue, we conducted a voxel-based morphometry and cerebrospinal fluid biomarker (α-synuclein, Aβ42, t-Tau and p-Tau) level correlation study in patients with DLB, AD and mixed cases (AD + DLB). Cerebrospinal fluid samples obtained by lumbar puncture and whole-brain T1-weighted images were collected in the AlphaLewyMA cohort. Within the cohort, 65 DLB patients, 18 AD patients, 24 AD + DLB patients and 16 neurological control subjects (NC) were clinically diagnosed. Correlation analyses were performed between cerebrospinal fluid biomarker levels and gray matter volumes using a voxel-based morphometry approach. A mediation analysis was performed to explore the role of gray matter volumes in the relationship between Aβ42 levels and clinical severity (MMSE scores). We observed a significant positive correlation between gray matter volumes and cerebrospinal fluid Aβ42 levels in the insula, the striatal regions, the right thalamus, and the claustrum in DLB patients (p < 0.05). Mediation analysis revealed that gray matter volumes significantly mediated the relationship between Aβ42 levels and MMSE scores in DLB patients. We found no significant correlation with gray matter volumes for α-synuclein, p-Tau or t-Tau in DLB patients (p < 0.05). We found no significant correlations in the AD, AD + DLB and NC groups for any of the biomarkers (p < 0.05). The specific correlation between a reduced cerebrospinal fluid Aβ42 level and lower gray matter volumes in insula, striatum, thalamus, and claustrum in DLB patients suggests a prominent role for amyloidopathy in promoting brain atrophy in key regions of the disease.
阿尔茨海默病（AD）和路易体痴呆（DLB）中蛋白病与神经退行性变之间的差异机制仍不清楚。为解决这一问题，我们对DLB、AD及混合病例（AD+DLB）患者进行了基于体素的形态学测量和脑脊液生物标志物（α-突触核蛋白、Aβ42、总tau蛋白和磷酸化tau蛋白）水平相关性研究。通过腰椎穿刺获取脑脊液样本，并在AlphaLewyMA队列中收集全脑T1加权图像。在该队列中，对65例DLB患者、18例AD患者、24例AD+DLB患者和16例神经科对照受试者（NC）进行了临床诊断。使用基于体素的形态学测量方法对脑脊液生物标志物水平与灰质体积之间进行相关性分析。进行中介分析以探讨灰质体积在Aβ42水平与临床严重程度（简易精神状态检查表[MMSE]评分）之间关系中的作用。我们观察到DLB患者脑岛、纹状体区域、右侧丘脑和屏状核的灰质体积与脑脊液Aβ42水平之间存在显著正相关（p<0.05）。中介分析显示，灰质体积在DLB患者Aβ42水平与MMSE评分之间的关系中起显著中介作用。我们发现DLB患者中α-突触核蛋白、磷酸化tau蛋白或总tau蛋白与灰质体积无显著相关性（p<0.05）。我们发现AD、AD+DLB和NC组中任何生物标志物均无显著相关性（p<0.05）。DLB患者脑脊液Aβ42水平降低与脑岛、纹状体、丘脑和屏状核灰质体积减少之间的特定相关性表明，淀粉样蛋白病变在促进该疾病关键区域脑萎缩中起重要作用。
