Loss of synaptic density in nucleus basalis of meynert indicates distinct neurodegeneration in Alzheimer’s disease: the RJNB-D study,European Journal of Nuclear Medicine and Molecular Imaging

当前位置： X-MOL 学术 › Eur. J. Nucl. Med. Mol. Imaging › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Loss of synaptic density in nucleus basalis of meynert indicates distinct neurodegeneration in Alzheimer’s disease: the RJNB-D study
European Journal of Nuclear Medicine and Molecular Imaging ( IF 8.6 ) Pub Date : 2024-08-08 , DOI: 10.1007/s00259-024-06862-z
Binyin Li ₁ , Haijuan Chen ₁ , Yingting Zheng ₁ , Xiaomeng Xu ₁ , Zhiwen You ₂ , Qi Huang ₃ , Yiyun Huang ₄ , Yihui Guan ₃ , Jun Zhao ₂ , Jun Liu _{1,

5} , Fang Xie ₃ , Jie Wang ₃ , Wei Xu ₁ , Junfang Zhang ₁ , Yulei Deng _{1,

5}

Affiliation

Background

The nucleus basalis of Meynert (NBM) is known to play a crucial role in the development and pathogenesis of Alzheimer’s Disease (AD), particularly the cholinergic system within the NBM. However, the relationship between synaptic loss in the NBM and the clinical profile of AD remains unclear.

Methods

In our study, we included 44 Aβ-negative normal controls (CN) and 76 Aβ-positive participants with cognitive impairment (CI). All participants underwent structural and diffusion magnetic resonance imaging (MRI), as well as positron emission tomography (PET) imaging to measure synaptic vesicle glycoprotein 2 A (SV2A) levels (Trial registration: NCT05623124. Registered 21 November 2022). The SV2A standardized uptake value ratios (SUVR) distribution in the NBM of CN participants was used as the reference norm. We investigated the association between NBM synaptic density and clinical performance, traditional AD biomarkers, and white matter tracts that passed the NBM.

Results

Participants with cognitive impairment (CI) who had NBM synaptic density below 1.5 standard deviations (SD) or 0.5 SD of the norm exhibited worse cognitive performance compared to cognitively normal (CN) individuals. Crucially, the extent of deviation in synaptic density from the norm was directly proportional to the severity of cognitive impairment and neurodegeneration biomarkers. Furthermore, among patients with cognitive impairment, synaptic loss in the NBM was associated with potential impairment in the density and organization of neurites within the white matter tracts connected to the NBM. Finally, neurite density index in the medial tracts may play a mediating role in the relationship between NBM synaptic density and MMSE scores.

Conclusion

The extent that synaptic density in NBM deviated from the norm suggested the extent of worse cognitive performance and severe neurodegeneration. Furthermore, cognitive impairment associated with synaptic loss in the NBM may be mediated by its pathological impact on NBM white matter tracts.

中文翻译：

Meynert 基底核突触密度的丧失表明阿尔茨海默病存在明显的神经退行性变：RJNB-D 研究

背景

众所周知，Meynert 基底核 (NBM) 在阿尔茨海默病 (AD) 的发展和发病机制中发挥着至关重要的作用，特别是 NBM 内的胆碱能系统。然而，NBM 突触丢失与 AD 临床特征之间的关系仍不清楚。

方法

在我们的研究中，我们纳入了 44 名 Aβ 阴性正常对照 (CN) 和 76 名患有认知障碍 (CI) 的 Aβ 阳性参与者。所有参与者均接受了结构和扩散磁共振成像 (MRI) 以及正电子发射断层扫描 (PET) 成像，以测量突触小泡糖蛋白 2 A (SV2A) 水平（试验注册：NCT05623124。2022 年 11 月 21 日注册）。 CN 参与者 NBM 中的 SV2A 标准化摄取值比率 (SUVR) 分布被用作参考规范。我们研究了 NBM 突触密度与临床表现、传统 AD 生物标志物以及通过 NBM 的白质束之间的关联。

结果

与认知正常 (CN) 个体相比，NBM 突触密度低于常模 1.5 个标准差 (SD) 或 0.5 SD 的认知障碍 (CI) 参与者表现出更差的认知表现。至关重要的是，突触密度偏离正常值的程度与认知障碍和神经退行性生物标志物的严重程度成正比。此外，在认知障碍患者中，NBM 突触损失与与 NBM 连接的白质束内神经突密度和组织的潜在损害相关。最后，内侧束神经突密度指数可能在 NBM 突触密度与 MMSE 评分之间的关系中起中介作用。