Regional metabolic alterations in Alzheimer's disease: an in vitro 1H NMR study of the hippocampus and cerebellum.

The concentrations of selected metabolites in the hippocampus and cerebellum of 13 Alzheimer's diseased (AD) and four nondemented postmortem brains were measured using high resolution 1H NMR spectroscopy. For both the hippocampal region and the cerebellum, the putative neuronal marker N-acetyl aspartate (NAA) was significantly lower in AD brains relative to the nondemented brains. For the hippocampal region, the NAA concentration correlated inversely with semiquantitative assessments of neuronal loss and neurofibrillary tangles. The gamma-aminobutyric acid levels in both hippocampus and cerebellum of an age- and a postmortem interval-matched subset of AD brains were lower than those of the controls. Because the cerebellum is generally thought to be unaffected by AD, the NAA decrease in the Alzheimer cerebellum may be due to lesions of either the Alzheimer or non-Alzheimer type in contralateral cerebrum.

An in vitro 1H nuclear magnetic resonance study of the temporoparietal cortex of Alzheimer brains.

The concentrations of selected metabolites in the posterior temporoparietal cortex of 13 Alzheimer's diseased (AD) and four nondemented postmortem brains (of individuals between the ages of 63 and 95) were determined using high-resolution 1H nuclear magnetic resonance (NMR) spectroscopy. The estimates for glutamate and inositol for AD brains did not show any statistically significant difference (P > 0.05) from those for the nondemented brains. The putative neuronal marker N-acetyl aspartate (NAA), creatine, and GABA were decreased in AD brains compared with the nondemented brains. The estimates for creatine, glutamate, and GABA showed significant linear correlations with those of NAA. Creatine, glutamate, GABA, and NAA appeared to be negatively correlated with the neurofibrillary tangles. Our results support a neuronal loss in the posterior temporoparietal cortices of AD brains.

In vivo 7Li NMR imaging and localized spectroscopy of rat brain.

Lithium-7 in vivo NMR spectroscopy and imaging techniques have been developed at 4.7 T for rat head. The pharmacokinetics of lithium (Li) uptake in rat head has been measured using STEAM localized spectroscopy for the whole brain, which showed relatively rapid uptake of Li and a steady level of Li from about 5 to 20 h. Localized spectroscopy on brain sections revealed no differences in Li concentration among the front, middle, and rear of the brain. The spin-lattice relaxation time showed a single exponential decay for the head. The spin-spin relaxation time for head showed a biexponential behavior. Using a 1H-7Li double coil assembly, 7Li images were generated for rat head, as was the corresponding 1H image for anatomic localization. The 7Li image (7-mm slice thickness, 4-mm in-plane resolution) recorded after the last dose in a multiple ip dose protocol shows the Li distribution in the head and neck. Based on 7Li images, the Li level in muscle was about twice that in the brain. Variations of 7Li intensity level across the brain were typically small.

Differentiation of human prostate cancer from benign hypertrophy by in vitro 1H NMR.

In vitro 1H NMR spectra were acquired for perchloric acid extracts of tissue samples of human prostate. Seven patients were diagnosed with prostate cancer, 13 with benign prostatic hypertrophy, and 3 with both conditions. Statistically significant differences between the cancer and benign groups were seen for the metabolite peak area ratios of citrate, creatine, and phosphorylcholine to alanine, and citrate to glutamate. There was no correlation of Gleason grade with any of the ratios measured for the cancer samples. Spectra from different sections of large tumors often yielded substantially different area ratios, confirming the heterogeneous nature of these prostate tumors.