Affiliations: [a] Shenzhen Key Laboratory of Drug Addiction, Shenzhen Neher Neural Plasticity Laboratory, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China
| [b]
University of Chinese Academy of Sciences, Beijing, China
| [c] Department of Neonatology, Shenzhen Maternity & Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Shenzhen, China
| [d] Department of Clinical Laboratory, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China. | [e] Department of Neurology, Shenzhen Luohu People’s Hospital; The Third Affiliated Hospital of Shenzhen University, Shenzhen, China
Correspondence:
[*]
Correspondence to: Dr. Qi Zhong, Department of Neurology, Shenzhen Luohu People’s Hospital, Shenzhen, China. E-mail: 13687329996@163.com and Dr. Yingjie Zhu, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, China. E-mail: yj.zhu1@siat.ac.cn.
Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is mainly characterized by cognitive deficits. Although many studies have been devoted to developing disease-modifying therapies, there has been no effective therapy until now. However, dietary interventions may be a potential strategy to treat AD. The ketogenic diet (KD) is a high-fat and low-carbohydrate diet with adequate protein. KD increases the levels of ketone bodies, providing an alternative energy source when there is not sufficient energy supply because of impaired glucose metabolism. Accumulating preclinical and clinical studies have shown that a KD is beneficial to AD. The potential underlying mechanisms include improved mitochondrial function, optimization of gut microbiota composition, and reduced neuroinflammation and oxidative stress. The review provides an update on clinical and preclinical research on the effects of KD or medium-chain triglyceride supplementation on symptoms and pathophysiology in AD. We also detail the potential mechanisms of KD, involving amyloid and tau proteins, neuroinflammation, gut microbiota, oxidative stress, and brain metabolism. We aimed to determine the function of the KD in AD and outline important aspects of the mechanism, providing a reference for the implementation of the KD as a potential therapeutic strategy for AD.
Keywords: Alzheimer’s disease, amyloid, dementia, ketogenic diet, ketone body, ketone bodies therapy, neuroinflammation, tau
protein
