In Alzheimer's disease (AD), defects in essential metabolic processes for energy supply and phospholipid membrane function have been implicated in the pathological process. However, post-mortem investigations are generally limited to late stage disease and prone to tissue decay artifacts. In vivo assessments of high energy phosphates, tissue pH and phospholipid metabolites are possible by phosphorus MR spectroscopy (31P-MRS), but so far only small studies, mostly focusing on single brain regions, have been performed. Therefore, we assessed phospholipid and energy metabolism in multiple brain regions of 31 early stage AD patients and 31 age- and gender-matched controls using 31P-MRS imaging. An increase of phosphocreatine (PCr) was found in AD patients compared with controls in the retrosplenial cortex, and both hippocampi, but not in the anterior cingulate cortex. While PCr/inorganic phosphate and pH were also increased in AD, no changes were found for phospholipid metabolites. This study showed that PCr levels are specifically increased in regions that show early degeneration in AD. Together with an increased pH, this indicates an altered energy metabolism in mild AD.
Keywords: 1H, proton; 31P–MRS, phosphorus magnetic resonance spectroscopy; AC, anterior commissure; ACC, anterior cingulate cortex; AD, Alzheimer's disease; ADP, adenosine diphosphate; ATP, adenosine triphosphate; Alzheimer's disease; CK, creatine kinase; CSF, cerebrospinal fluid; Cr, creatine; Dementia; Energy metabolism; GM, grey matter; GPCh, glycerophosphocholine; GPEth, glycerophosphoethanolamine; HL, left hippocampus; HR, right hippocampus; LS, least square; MCI, mild cognitive impairment; MMSE, Mini Mental State Examination; MRSI, magnetic resonance spectroscopic imaging; NAD(H), nicotinamide adenine dinucleotide; OXPHOS, oxidative phosphorylation; PC, posterior commissure; PCh, phosphocholine; PCr, phosphocreatine; PDE, phosphodiesters; PEth, phosphoethanolamine; PME, phosphomonoesters; Phospholipid metabolism; Phosphorus magnetic resonance spectroscopic imaging; Pi, inorganic phosphate; ROI, region of interest; RSC, retrosplenial cortex; WM, white matter.