Spotorno Nicola, Najac Chloé, Strandberg Olof, Stomrud Erik, van Westen Danielle, Nilsson Markus, Ronen Itamar, Hansson Oskar
Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Lund 22184, Sweden.
Department of Radiology, C.J. Gorter MRI Center, Leiden University Medical Center, Leiden 2333, The Netherlands.
Brain Commun. 2024 Feb 1;6(1):fcae026. doi: 10.1093/braincomms/fcae026. eCollection 2024.
In Alzheimer's disease, reconfiguration and deterioration of tissue microstructure occur before substantial degeneration become evident. We explored the diffusion properties of both water, a ubiquitous marker measured by diffusion MRI, and -acetyl-aspartate, a neuronal metabolite probed by diffusion-weighted magnetic resonance spectroscopy, for investigating cortical microstructural changes downstream of Alzheimer's disease pathology. To this aim, 50 participants from the Swedish BioFINDER-2 study were scanned on both 7 and 3 T MRI systems. We found that in cognitively impaired participants with evidence of both abnormal amyloid-beta (CSF amyloid-beta42/40) and tau accumulation (tau-PET), the -acetyl-aspartate diffusion rate was significantly lower than in cognitively unimpaired participants ( < 0.05). This supports the hypothesis that intraneuronal tau accumulation hinders diffusion in the neuronal cytosol. Conversely, water diffusivity was higher in cognitively impaired participants ( < 0.001) and was positively associated with the concentration of myo-inositol, a preferentially astrocytic metabolite ( < 0.001), suggesting that water diffusion is sensitive to alterations in the extracellular space and in glia. In conclusion, measuring the diffusion properties of both water and -acetyl-aspartate provides rich information on the cortical microstructure in Alzheimer's disease, and can be used to develop new sensitive and specific markers to microstructural changes occurring during the disease course.
在阿尔茨海默病中，组织微观结构的重构和退化在实质性变性明显出现之前就已发生。我们探究了水（通过扩散加权磁共振成像测量的一种普遍存在的标志物）和N-乙酰天门冬氨酸（通过扩散加权磁共振波谱探测的一种神经元代谢物）的扩散特性，以研究阿尔茨海默病病理下游的皮质微观结构变化。为此，对瑞典BioFINDER-2研究中的50名参与者在7T和3T磁共振成像系统上进行了扫描。我们发现，在有异常淀粉样蛋白β（脑脊液淀粉样蛋白β42/40）和tau蛋白积累（tau正电子发射断层扫描）证据的认知受损参与者中，N-乙酰天门冬氨酸的扩散速率显著低于认知未受损参与者（P<0.05）。这支持了神经元内tau蛋白积累阻碍神经元胞浆扩散的假说。相反，认知受损参与者中的水扩散率更高（P<0.001），且与肌醇（一种优先存在于星形胶质细胞中的代谢物）浓度呈正相关（P<0.001），这表明水扩散对细胞外空间和神经胶质细胞的改变敏感。总之，测量水和N-乙酰天门冬氨酸的扩散特性可提供有关阿尔茨海默病皮质微观结构的丰富信息，并可用于开发针对疾病过程中发生的微观结构变化的新型敏感且特异的标志物。
