Dynamical modelling of the effects of medium-chain triglycerides on cerebral ketone body metabolism

• Main Author: Espina, Abigail R.
• Format: text
• Language: English
• Published: Animo Repository 2023
• Subjects: Alzheimer's disease; Ketone body metabolism; Mathematics
• Online Access: https://animorepository.dlsu.edu.ph/etdm_math/8; https://animorepository.dlsu.edu.ph/cgi/viewcontent.cgi?article=1007&context=etdm_math
• Institution: De La Salle University

Alzheimer’s Disease (AD) is a neurodegenerative disorder that causes severe structural brain atrophy and affects multiple brain functions. Cerebral glucose hypometabolism, associated with senile plaque density formation, is a pre-symptomatic feature of AD and significantly contributes to AD’s future development and progression. Due to advanced aging, the cerebral glucose metabolism rate (CGMR) gradually slows down. Furthermore, AD patients experience a more drastic CGMR decline, leading to a wide brain energy gap. To bridge the increasing brain energy gap, ketone bodies (KBs) are used as a supplementary source of energy as cerebral KB metabolism remains unaffected in AD patients. Ketogenic interventions such as Medium-Chain Triglyceride (MCT)-induced treatment can help augment the brain’s energy source availability and might delay further cognitive decline. With this, we constructed a mathematical model on the simplified biochemical pathways of cerebral glucose and KB metabolism to illustrate the effects of glucose hypometabolism on healthy aging individuals and Mild Cognitive Impairment (MCI) and AD patients. Through the generated simulations, we have verified that KB concentration levels rise during prolonged fasting, and in consideration of glucose hypometabolism, MCT-induced intervention increases the concentration levels of acetyl-CoA (AC) in AD patients. Furthermore, MCT-induced supplement helps increase the AC concentration levels in healthy adults without pharmacotherapy under normal conditions.