Betahydroxybutyrate Consumption in Autopsy Brain Tissue from Alzheimer's Disease Subjects.

Abstract

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.