Imaging and spectroscopic approaches to probe brain energy metabolism dysregulation in neurodegenerative diseases

Changes in energy metabolism are generally considered to play an important role in neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. Whether these changes are causal or simply a part of self-defense mechanisms is a matter of debate. Furthermore, energy defects have often been discussed solely in the context of their probable neuronal origin without considering the cellular heterogeneity of the brain. Recent data point towards the existence of a tri-cellular compartmentation of brain energy metabolism between neurons, astrocytes, and oligodendrocytes, each cell type having a distinctive metabolic profile. Still, the number of methods to follow energy metabolism in patients is extremely limited and existing clinical techniques are blind to most cellular processes. There is a need to better understand how brain energy metabolism is regulated in health and disease through experiments conducted at different scales in animal models to implement new methods in the clinical setting. The purpose of this review is to offer a brief overview of the broad spectrum of methodological approaches that have emerged in recent years to probe energy metabolism in more detail. We conclude that multi-modal neuroimaging is needed to follow non-cell autonomous energy metabolism dysregulation in neurodegenerative diseases.