Document Type

Journal Article

Publication Title

Frontiers in Neuroscience




Frontiers Media S.A.


School of Medical and Health Sciences




Ramezani, M., Fernando, M., Eslick, S., Asih, P. R., Shadfar, S., Bandara, E. M.S., . . . Martins, R. N. (2023). Ketone bodies mediate alterations in brain energy metabolism and biomarkers of Alzheimer’s disease. Frontiers in Neuroscience, 17, article 1297984.


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 () plaques and neurofibrillary tangles containing the neuron-specific protein tau is associated with changes in fluid biomarkers including A , 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 A , tau (mainly p-tau 181), GFAP, and NFL, and discusses the role of KBs on neuroinflammation, oxidative stress, and mitochondrial metabolism.



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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.