In vivo evidence for cerebral depletion in high-energy phosphates in progressive supranuclear palsy

Indirect evidence from laboratory studies suggests that mitochondrial energy metabolism is impaired in progressive supranuclear palsy(PSP), but brain energy metabolism has not yet been studied directly in vivo in a comprehensive manner in patients. We have used combined phosphorus and proton magnetic resonance spectroscopy to measure adenosine-triphosphate(ATP), adenosine-diphosphate(ADP), phosphorylated creatine, unphosphorylated creatine, inorganic phosphate and lactate in the basal gangliaand the frontal and occipital lobesof clinically probable patients (N= 21; PSP stages II to III) and healthy controls (N= 9). In the basal ganglia, which are severely affected creatinein PSP patients, the concentrations of high-energy phosphates(= ATP + phosphorylated creatine) and inorganic phosphate, but not low-energy phosphates (=ADP+ unphosphorylated creatine), were decreased. The decrease probably does not reflect neuronal death, as the neuronal marker N-acetylaspartatewas not yet significantly reduced i...