應用擴散磁振造影技術探討阿茲海默動物模型腦部結構性連結的進程與深腦電刺激治療潛力

Abstract

阿茲海默症是少數無法治癒、預防、減緩的主要死因之一。隨著平均壽命增加，此疾病的盛行率也隨之增加。深腦電刺激藉由增強或阻斷不同腦區之前連結已被證實可治療多種神經疾病。穹窿因為與海馬迴之間的連結，因此有希望為深腦電刺激的目標腦區來治療阿茲海默症。儘管目前已經有研究及試驗，但尚未真正了解深腦電刺激穹窿使阿茲海默症病人有正向表現的原因。在此研究中，使用阿茲海默症基因轉殖老鼠模型及擴散磁振造影技術來了解白質在疾病中的長期變化。阿茲海默症老鼠模型在約年紀六個月時，減少非等向性指標及行為的表現。透過磁振相容探針及動物模型，觀察到深腦電刺激的時機使治療成果上有所差異。阿茲海默症老鼠模型在穹窿進行深腦電刺激對於非等向性指標及行為表現上有改善。

Alzheimer’s disease (AD) is one of the major causes of death that currently cannot be cured, prevented, or slowed. Due to the rising survival age, the upward trend of the disease prevalence will continue. Deep brain stimulation (DBS) has proven to be a viable therapy for various neurological disorders, by enhancing or interrupting different connections within the brain. Various brain structures have been considered as the target for DBS, including the fornix. DBS of the fornix, a major output tract of the hippocampus, has been shown to be a promising target for DBS therapy in AD patients. Even though these studies and trials are taking place, it is still not well understood what alterations are resulting in positive changes within AD patients. In this study, a triple-transgenic (3xTg) mouse model of AD was used in order to understand the longitudinal changes of white matter over the course of the disease through the use of diffusion tensor imaging (DTI). The 3xTg mouse model showed to have decreased FA values and behavioral performance around the age of 6 months. Through the integration of a MR compatible probe and the 3xTg model, it was observed that the timing of the implantation of DBS stimulation probes and stimulation therapy makes a difference in the effectiveness of the therapy. DBS of the fornix showed improvement in the behavior of 3xTg mice and FA values.