31P Nuclear Magnetic Resonance Study of the Brain in Alzheimerʼs Disease

Pettegrew, Jay W.; Moossy, John; Withers, Gregory P.; McKeag, Dennis; Panchalingam, K.

doi:10.1097/00005072-198805000-00004

Cited by 144 publications

(37 citation statements)

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“…In other brain regions, significant decreases in phosphoethanolamine have been described (21,26). These prior reports and our current data contradict the reported increase of phosphomonoesters in AD brain measured by 31P NMR spectroscopy (5). One explanation for the divergent results might be time dependence: phosphomonoester levels might be elevated only in the intermediate stage but become normal in the late and end stages of AD (3).…”

contrasting

confidence: 76%

“…Cell membrane lipid abnormalities have been described in AD brain, and it has been hypothesized that these contribute to amyloid deposition (1,2) and neuronal dysfunction (3). Initial evidence for a biochemical abnormality in the metabolism of phospholipids came from in vitro 31P NMR spectroscopic studies showing that the ratio of glycerophosphocholine (GPC) to glycerophosphoethanolamine (GPE) as well as levels of glycerophosphodiesters and phosphomonoesters were increased in AD brain (4)(5)(6). Quantitative HPLC analysis has demonstrated that the increase in glycerophosphodiesters was due to accumulation of the phospholipid catabolites GPC and GPE (7,8).…”

mentioning

confidence: 99%

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Evidence for a membrane defect in Alzheimer disease brain.

Nitsch

Blusztajn

Pittas

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

486

267

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To determine whether neurodegeneration in Alzheimer disease brain is associated with degradation of structural cell membrane molecules, we measured tissue levels of the major membrane phospholipids and their metabolites in three cortical areas from postmortem brains of Alzheimer disease patients and matched controls. Among phospholipids, there was a significant (P < 0.05) decrease in phosphatidylcholine and phosphatidylethanolamine. There were significant (P < 0.05) decreases in the initial phospholipid precursors choline and ethanolamine and increases in the phospholipid deacylation product glycerophosphocholine. The ratios of glycerophosphocholine to choline and glycerophosphoethanolamine to ethanolamine were significantly increased in all examined Alzheimer disease brain regions. The activity of the glycerophosphocholine-degrading enzyme glycerophosphocholine cholinephosphodiesterase was normal in Alzheimer disease brain. There was a near stoichiometric relationship between the decrease in phospholipids and the increase of phospholipid catabolites. These data are consistent with increased membrane phospholipid degradation in Alzheimer disease brain. Similar phospholipid abnormalities were not detected in brains of patients with Huntington disease, Parkinson disease, or Down syndrome. We conclude that the phospholipid abnormalities described here are not an epiphenomenon of neurodegeneration and that they may be specific for the pathomechanism of Alzheimer disease.Brain lesions characteristic of Alzheimer disease (AD) include amyloid deposition, the formation of neurofibrillary tangles, and neuronal degeneration. The etiology and pathophysiology of neuronal death in AD are unknown. Cell membrane lipid abnormalities have been described in AD brain, and it has been hypothesized that these contribute to amyloid deposition (1, 2) and neuronal dysfunction (3). Initial evidence for a biochemical abnormality in the metabolism of phospholipids came from in vitro 31P NMR spectroscopic studies showing that the ratio of glycerophosphocholine (GPC) to glycerophosphoethanolamine (GPE) as well as levels of glycerophosphodiesters and phosphomonoesters were increased in AD brain (4-6). Quantitative HPLC analysis has demonstrated that the increase in glycerophosphodiesters was due to accumulation of the phospholipid catabolites GPC and GPE (7, 8). The biochemical mechanisms accounting for the increase of phospholipid catabolites are unknown. To investigate the abnormalities in the phospholipid metabolic pathways, we examined levels of the parent phospholipids, their precursors, and their catabolites (see Fig. 1) in three cortical brain areas obtained at autopsy from AD patients and matched controls. To rule out the possibility that the elevation in GPC reflects a slowing in its degradation,

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contrasting

confidence: 76%

mentioning

confidence: 99%

Evidence for a membrane defect in Alzheimer disease brain.

Nitsch

Blusztajn

Pittas

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

486

267

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“…in the region of interest ( Table 1). The product of MRS is a ''spectrum'' with a frequency axis in parts per million (ppm) and a signal amplitude axis (22)(23)(24)(25)(26)(27)(28). The signal amplitude (area) is a measure of a particular metabolite concentration.…”

Section: The Basics Of Mrsmentioning

confidence: 99%

“…The peak amplitude (area) that is directly related to the concentration of that assigned metabolite is displaced along the Y axis. In vivo 1 H-MRS and 31 P-MRS are the most widely used applications of MRS, but other atoms that are used for MRS studies include 13 C, 15 N, 19 F, and 23 Na. Major metabolites detected by 1 …”

Section: The Basics Of Mrsmentioning

confidence: 99%

“…Choline (Cho), an indicator of membrane activity, is often elevated in the presence of malignant processes. 23 Na Sodium 3 2 16.89 0.0925 100 31 P Phosphorus 1 2 25.85 0.0663 100 35 Cl Chlorine 3 2 6.26 0.0047 75.53 39 K Potassium 3 2 2.98 0.00051 93.08 Myo-inositol (mI), a sugar alcohol, is a marker of astrocytic activity and is often higher in conditions such as AD and malignant tumors.…”

Section: H Mrs Are As Followsmentioning

confidence: 99%

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Magnetic resonance spectroscopy (MRS) and its application in Alzheimer's disease

Mandal

2007

Concepts Magnetic Resonance

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Magnetic resonance spectroscopy (MRS) is a noninvasive tool to measure the chemical composition of tissues (in vivo) and characterize functional metabolic processes in different parts of the human organs. It provides vital biological information at the molecular level. Combined with magnetic resonance imaging (MRI), an integrated MRI/MRS examination provides anatomical structure, pathological function, and biochemical information about a living system. MRS provides a link between the biochemical alterations and the pathophysiology of disease. This article provides a comprehensive description of the MRS technique and its application in Alzheimer's disease (AD) research. This review is a primer for students and researchers seeking a firm theoretical understanding of MRS physics as well as its application in clinical AD research.

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