Betahydroxybutyrate Consumption in Autopsy Brain Tissue from Alzheimer’s Disease Subjects

Background Alzheimer's disease (AD) features perturbed brain glucose utilization, which could contribute to brain bioenergetic failure. This led some to consider using ketone bodies to enhance AD brain bioenergetics and treat AD. Objective We evaluated the rate at which brain homogenates from persons with Alzheimer's disease (AD) metabolize D-β-hydroxybutyrate (BHB). Methods We homogenized pieces of temporal cortex from frozen autopsy brains obtained from recently deceased AD subjects (n = 4), and age-matched subjects that did not have clinical AD (n = 3). Measuring the rate of CO2 production that followed the introduction of radiolabeled BHB to the homogenates yielded a BHB utilization rate. Results Compared to the control homogenates, the BHB-supported CO2 production rate was 66%lower in the AD homogenates (p < 0.05). Conclusions AD brains can utilize BHB, albeit less robustly than control brains. In conjunction with a previous study that demonstrated reduced glucose utilization in AD brain homogenates, our BHB data provide further evidence of AD brain mitochondrial dysfunction or altered mitochondrial biology.