The brain primarily relies on glucose as its main energy source under normal physiological conditions due to its high metabolic demand and limited capacity to store energy. Unlike other tissues, the brain's ability to metabolize fatty acids is minimal because of the blood-brain barrier and low levels of enzymes required for fatty acid oxidation. While ketone bodies can serve as an alternative during prolonged fasting or starvation, glucose remains the essential fuel for maintaining neuronal function and synaptic activity. Efficient glucose uptake and metabolism are critical for sustaining cognitive processes and overall brain health.

Reference: Principles of Neural Science, Kandel et al., 5th Edition.