Multinuclear magnetic resonance spectroscopy for in vivo assessment of mitochondrial dysfunction in Parkinson's disease

Parkinson's disease (PD) is a common and often devastating neurodegenerative disease affecting up to one million individuals in the United States alone. Multiple lines of evidence support mitochondrial dysfunction as a primary or secondary event in PD pathogenesis; a better understanding, therefore, of how mitochondrial function is altered in vivo in brain tissue in PD is a critical step toward developing potential PD biomarkers. In vivo study of mitochondrial metabolism in human subjects has previously been technically challenging. However, proton and phosphorus magnetic resonance spectroscopy (¹H and ³¹P MRS) are powerful noninvasive techniques that allow evaluation in vivo of lactate, a marker of anaerobic glycolysis, and high energy phosphates, such as adenosine triphosphate and phosphocreatine, directly reflecting mitochondrial function. This article reviews previous ¹H and ³¹P MRS studies in PD, which demonstrate metabolic abnormalities consistent with mitochondrial dysfunction, and then presents recent ¹H MRS data revealing abnormally elevated lactate levels in PD subjects.