title: In vivo evidence for cerebral depletion in high-energy phosphates in progressive supranuclear palsy.
abstract: 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 ganglia and the frontal and occipital lobes of clinically probable patients (N=21; PSP stages II to III) and healthy controls (N=9). In the basal ganglia, which are severely affected creatine in 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-acetylaspartate was not yet significantly reduced in the early-stage patients examined. The frontal lobe, also prone to neurodegeneration in PSP, showed similar alterations, whereas the occipital lobe, typically unaffected, showed less pronounced alterations. The levels of lactate, a product of anaerobic glycolysis, were elevated in 35% of the patients. The observed changes in the levels of cerebral energy metabolites in PSP are consistent with a functionally relevant impairment of oxidative phosphorylation.
authors.affiliation: Department of Neurology, Philipps University, Marburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Stamelou
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pilatus
authors.forename: Alexander
authors.initials: A
authors.lastname: Reuss
authors.forename: Jörg
authors.initials: J
authors.lastname: Magerkurth
authors.forename: Karla M
authors.initials: KM
authors.lastname: Eggert
authors.forename: Susanne
authors.initials: S
authors.lastname: Knake
authors.forename: Merle
authors.initials: M
authors.lastname: Ruberg
authors.forename: Carmen
authors.initials: C
authors.lastname: Schade-Brittinger
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.forename: Günter U
authors.initials: GU
authors.lastname: Höglinger
mesh_terms: D000244:Adenosine Diphosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000368:Aged; D000369:Aged, 80 and over; D001479:Basal Ganglia / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D003401:Creatine / Q000032:analysis; D004734:Energy Metabolism; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008875:Middle Aged; D009778:Occipital Lobe / Q000378:metabolism; D010710:Phosphates / Q000032:analysis; D010725:Phosphocreatine / Q000032:analysis; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism*
chemical_list: D010710:Phosphates; D010725:Phosphocreatine; D019344:Lactic Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003401:Creatine