Abstract:
Alzheimer\'s disease (AD) is the most common form of dementia. AD is a progressive neurodegenerative disorder characterized by cognitive dysfunction, including learning and memory deficits, and behavioral changes. Neuropathology hallmarks of AD such as amyloid beta (Aβ) plaques and neurofibrillary tangles containing the neuron-specific protein tau is associated with changes in fluid biomarkers including Aβ, phosphorylated tau (p-tau)-181, p-tau 231, p-tau 217, glial fibrillary acidic protein (GFAP), and neurofilament light (NFL). Another pathological feature of AD is neural damage and hyperactivation of astrocytes, that can cause increased pro-inflammatory mediators and oxidative stress. In addition, reduced brain glucose metabolism and mitochondrial dysfunction appears up to 15 years before the onset of clinical AD symptoms. As glucose utilization is compromised in the brain of patients with AD, ketone bodies (KBs) may serve as an alternative source of energy. KBs are generated from the β-oxidation of fatty acids, which are enhanced following consumption of ketogenic diets with high fat, moderate protein, and low carbohydrate. KBs have been shown to cross the blood brain barrier to improve brain energy metabolism. This review comprehensively summarizes the current literature on how increasing KBs support brain energy metabolism. In addition, for the first time, this review discusses the effects of ketogenic diet on the putative AD biomarkers such as Aβ, tau (mainly p-tau 181), GFAP, and NFL, and discusses the role of KBs on neuroinflammation, oxidative stress, and mitochondrial metabolism.
摘要:
阿尔茨海默病(AD)是最常见的痴呆形式。AD是一种以认知功能障碍为特征的进行性神经退行性疾病,包括学习和记忆缺陷,和行为变化。AD的神经病理学标志,如淀粉样β(Aβ)斑块和含有神经元特异性蛋白tau的神经原纤维缠结与包括Aβ在内的液体生物标志物的变化有关。磷酸化tau(p-tau)-181,p-tau231,p-tau217,胶质纤维酸性蛋白(GFAP),和神经丝光(NFL)。AD的另一个病理特点是神经毁伤和星形胶质细胞过度活化,这可能导致促炎介质和氧化应激增加。此外,在临床AD症状发作前15年出现脑葡萄糖代谢降低和线粒体功能障碍。由于AD患者大脑中的葡萄糖利用受到损害,酮体(KBs)可以作为替代能源。KBs是由脂肪酸的β-氧化产生的,在食用高脂肪的生酮饮食后,中等蛋白质,低碳水化合物。已显示KBs穿过血脑屏障以改善脑能量代谢。这篇综述全面总结了当前有关增加KBs如何支持大脑能量代谢的文献。此外,第一次,这篇综述讨论了生酮饮食对推定的AD生物标志物如Aβ,tau(主要是p-tau181),GFAP,和NFL,并讨论了KBs在神经炎症中的作用,氧化应激,和线粒体代谢.