PDF(Pubmed)
Abstract：
Many lines of evidence suggest that mitochondria have a central role in aging-related neurodegenerative diseases, such as Alzheimer\'s disease (AD). Mitochondrial dysfunction, cerebral energy dysmetabolism and oxidative damage increase with age, and are early event in AD pathophysiology and may precede amyloid beta (Aβ) plaques. In vivo probes of mitochondrial function and energy metabolism are therefore crucial to characterize the bioenergetic abnormalities underlying AD risk, and their relationship to pathophysiology and cognition. A majority of the research conducted in humans have used 18F-fluoro-deoxygluose (FDG) PET to image cerebral glucose metabolism (CMRglc), but key information regarding oxidative phosphorylation (OXPHOS), the process which generates 90% of the energy for the brain, cannot be assessed with this method. Thus, there is a crucial need for imaging tools to measure mitochondrial processes and OXPHOS in vivo in the human brain. 31Phosphorus-magnetic resonance spectroscopy (31P-MRS) is a non-invasive method which allows for the measurement of OXPHOS-related high-energy phosphates (HEP), including phosphocreatine (PCr), adenosine triphosphate (ATP), and inorganic phosphate (Pi), in addition to potential of hydrogen (pH), as well as components of phospholipid metabolism, such as phosphomonoesters (PMEs) and phosphodiesters (PDEs). Herein, we provide a systematic review of the existing literature utilizing the 31P-MRS methodology during the normal aging process and in patients with mild cognitive impairment (MCI) and AD, with an additional focus on individuals at risk for AD. We discuss the strengths and limitations of the technique, in addition to considering future directions toward validating the use of 31P-MRS measures as biomarkers for the early detection of AD.
摘要：
许多证据表明，线粒体在衰老相关的神经退行性疾病中起着核心作用，如阿尔茨海默病（AD）。线粒体功能障碍,脑能量代谢异常和氧化损伤随年龄增加,是AD病理生理学的早期事件，可能先于淀粉样蛋白β（Aβ）斑块。因此，线粒体功能和能量代谢的体内探针对于表征AD风险的生物能异常至关重要。以及它们与病理生理学和认知的关系。在人类中进行的大多数研究都使用18F-氟脱氧葡萄糖（FDG）PET来成像脑葡萄糖代谢（CMRglc），但是关于氧化磷酸化（OXPHOS）的关键信息，为大脑产生90%能量的过程，不能用这种方法评估。因此，迫切需要成像工具来测量人脑体内的线粒体过程和OXPHOS。31磷磁共振波谱（31P-MRS）是一种非侵入性方法，可以测量与OXPHOS相关的高能磷酸盐（HEP），包括磷酸肌酸（PCr），三磷酸腺苷（ATP），和无机磷酸盐(Pi)，除了氢的电势（pH），以及磷脂代谢的成分，例如磷酸单酯(PME)和磷酸二酯(PDEs)。在这里，我们提供了在正常衰老过程中以及轻度认知障碍（MCI）和AD患者中使用31P-MRS方法的现有文献的系统综述，另外关注有AD风险的个人。我们讨论了该技术的优点和局限性，除了考虑未来的方向，以验证31P-MRS措施作为早期发现AD的生物标志物的使用。
