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In Vitro31P NMR Spectroscopy Detects Altered Phospholipid Metabolism in Alzheimer's Disease

Published online by Cambridge University Press:  18 September 2015

Orietta Miatto ,
R. Gilberto Gonzalez ,
Ferdinando Buonanno  and
John H. Growdon
Orietta Miatto*
Affiliation:
Massachusetts General Hospital, Boston, MA
R. Gilberto Gonzalez
Affiliation:
Massachusetts Institute of Technology, Cambridge, MA
Ferdinando Buonanno
Affiliation:
Massachusetts General Hospital, Boston, MA
John H. Growdon
Affiliation:
Massachusetts General Hospital, Boston, MA
*
Massachusetts General Hospital, Boston, MA 02114, U.S.A.
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Abstract:

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In order to study possible metabolic derangements in Alzheimer's disease (AD), we performed phosphorus 31 nuclear magnetic resonance (31P NMR) spectroscopy on brain samples obtained at autopsy from 7 patients with AD and 9 control subjects. Aqueous solutions of brain tissue contained well-defined peaks of intermediate compounds in phospholipid metabolism, including the phosphomonoesters phosphocholine and phosphoethanolamine, and the phosphodiesters glycerophosphorylcholine and glycerophosphorylethanolamine. 3IP NMR spectra also displayed the inorganic phosphorus signal, which provides an index to the in vivo concentration of high-energy compounds.

We found evidence for altered phospholipid metabolism in that relative levels of phosphomonoesters were decreased, and phosphodiesters increased, in frontal and parietal regions of patients with AD compared to control subjects. The inorganic phosphorus resonance peaks were similar in AD and control subjects, suggesting that energy stores are not diminished in AD. These preliminary data are consistent with the hypothesis that abnormalities in phospholipid metabolism contribute to possible neuronal membrane dysfunction and impaired cholinergic neurotransmission in AD.

Type
Imaging of Demented Subjects
Information
Canadian Journal of Neurological Sciences , Volume 13 , Issue S4 , November 1986 , pp. 535 - 539
Copyright
Copyright © Canadian Neurological Sciences Federation 1986

References

1.Besson, JA, Corrigan, FM, Foreman, EI, et al. Differentiating senile dementia of Alzheimer type and multi-infarct dementia by proton NMR imaging. Lancet 2 1983; 789.CrossRefGoogle ScholarPubMed
2.Besson, JA, Corrigan, FM, Foreman, EI, et al. Nuclear magnetic resonance (NMR). II Imaging in dementia. Brit J Psychiat 1985; 146: 31–35.CrossRefGoogle ScholarPubMed
3.Besson, JA, Corrigan, FM, Foreman, EI, et al. Proton NMR parameters and dementia. Progress in Nuclear Medicine 1984; 8: 94–99.Google ScholarPubMed
4.Besson, JA, Foreman, EI, Eastwood, LM, et al. Cognitive evaluation following NMR imaging of the brain. J Neurol Neurosurg Psychiatr 1984; 47: 314–316.CrossRefGoogle ScholarPubMed
5.Besson, JA, Glen, AI, MacDonald, A, et al. Nuclear magnetic resonance observations in alcoholic cerebral disorder and the role of vasopressin. Lancet 2 1981, 923–924.Google ScholarPubMed
6.Brant-Zawadzki, M, Fein, G, Van-Dyke, C, et al. MR imaging of the aging brain: patchy white-matter lesions and dementia. Am J. Neurol Res 1985; 6(5): 675–682.Google ScholarPubMed
7.DeWitt, LD, Grek, AH, Buonanno, FS, et al. MRI and the study of aphasia. Neurology 1985; 35: 861–865.CrossRefGoogle Scholar
8.Erkinjuntti, T, Sipponen, JT, Iivanainen, M, et al. Cerebral NMR and CT imaging in dementia. J Computer Assisted Tomography 1984; 8: 614–618.CrossRefGoogle ScholarPubMed
9.Kinkel, WR, Jacobs, L, Polachini, I, et al. Subcortical arteriosclerotic encephalopathy (Binswanger’s disease). Computed tomographic, nuclear magnetic resonance, and clinical correlations. Arch Neurol 1985; 42: 951–959.CrossRefGoogle ScholarPubMed
10.Kovanen, J, Erkinjuntti, T, Iivanainen, M, et al. Cerebral MR and CT imaging in Creutzfeldt-Jakob disease. J Computer Assisted Tomography 1985; 9(1): 125–128.CrossRefGoogle ScholarPubMed
11.Johnson, K, Buonanno, F, Davis, K, et al. Comparison of magnetic resonance (MR) and x-ray computed tomography (CT) in dementia. Neurology 1986; 36 (Suppl 1): 265.Google Scholar
12.Growdon, JH, Corkin, S, Buonanno, F, et al. Diagnostic methods in Alzheimer’s disease: magnetic resonance brain imaging and CSF neurotransmitter markers. In: Fisher, A, Hanin, I, Lachman, C. eds. Alzheimer’s and Parkinson’s Disease. Strategies in Research and Development. New York: Plenum Press 1986: 191–204.CrossRefGoogle Scholar
13.Glonek, T, Kopp, SH, Kot, E.et al. 31-P nuclear magnetic resonance analysis of brain: the perchloric acid extract spectrum. J Neurochem 1982; 39: 1210–1219.CrossRefGoogle Scholar
14.Burt, CT, Glonek, R, Barany, R.Analysis of phosphate metabolites, the intracellular pH and the state of adenosine triphosphate in intact muscle by phosphorus nuclear magnetic spectroscopy. J Biol Chem 1982; 251: 2584.CrossRefGoogle Scholar
15.Rouser, G, Yamamoto, A, Kritchevsky, G.Lipids of the nervous system: changes with age, species variation, lipid class relationships, and comparison of brain to other organs. In: Paoletta, R, Davison, AN, eds. Chemistry and Brain Development. New York: Plenum Press, 1971: 91–109.CrossRefGoogle Scholar
16.Hirata, F, Axelrod, J.Phospholipid methylation and biological signal transmission. Science 1980; 209: 1082–1090.CrossRefGoogle ScholarPubMed
17.Blusztajn, JK, Wurtman, RH.Choline and cholinergic neurons. Science 1983; 221: 614–620.CrossRefGoogle ScholarPubMed
18.Behar, KL, denHollander, JA, Petroff, OAC, et al. Effect of hypoglycemic encephalopathy upon amino acids, high-energy phosphates, and pH in the rat brain in vivo: detection by sequential 1H and 31P NMR spectroscopy. J Neurochem 1985; 44: 1045–1055.CrossRefGoogle Scholar
19.Bendall, MR.In: James, TL, Margulis, AR, eds. Biochemical Magnetic Resonance. San Francisco CA. Radiology Research and Education Foundation, 1984: 99.Google Scholar
20.Bottomley, PA, Edelstein, WA, Foster, TH, et al. In vivo solvent surpressed localized hydrogen nuclear magnetic resonance spectroscopy: a window to metabolism? Proceedings of National Academy of Sciences USA 1985; 82: 2148–2152.CrossRefGoogle Scholar
21.Bottomley, PA, Kogure, K, Namon, R.et al. Cerebral energy metabolism in rats studied by phosphorus nuclear magnetic resonance using surface coils. Magnetic Resonance Imaging 1982; 1: 81–85.CrossRefGoogle ScholarPubMed
22.Brenton, DP, Garrod, PJ, Krywawych, S.et al. Phosphoethanolamine is a major constituent of phosphomonoester peak detected by 31 NMR in newborn brain. Lancet 1 1985; 115.CrossRefGoogle Scholar
23.Gadian, DG, Nuclear Magnetic Resonance and Its Application to Living Systems. Tayler, DJ, Bore, PJ, Syles, P, et al, eds. Oxford. Oxford Univ Press. Molecular Biological Medicine 1982; 1: 77.Google Scholar
24.Gyulai, L, Bolinger, L, Leigh, JS Jr, et al. Phosphorylethanolamine —the major constituent of the phosphomonoester peak observed by 31P NMR on developing dog brain. FEBS Letters 1984; 178: 137–142.CrossRefGoogle ScholarPubMed
25.Radda, GK, Bore, PJ, Rajagopalan, B.Clinical aspects on 31P NMR spectroscopy. Brit Med Bull 1984; 40: 155–159.CrossRefGoogle Scholar
26.Taylor, DJ, Bore, PJ, Styles, P, et al. Bioenergetics of intact human muscle: a31P nuclear magnetic resonance study. Molecular Biological Medicine 1983; 1: 77–94.Google Scholar
27.Pettegrew, JW, Minshew, NJ, Cohen, NM, et al. 31-P changes in Alzheimer’s and Huntington’s disease brain. Neurology 1984; 34: 281.Google Scholar
28.Burt, CT, Ribolow, HJJ.A hypothesis: noncyclic phosphodiesters may play a role in membrane control. Biochem Med 1984: 31: 21–30.CrossRefGoogle ScholarPubMed
29.Seeley, PJ, Busby, SJW, Gadian, DG, et al. A new approach to metabolite compartmentation in muscle. Trans Biochem Soc 1976; 4: 62–64.CrossRefGoogle ScholarPubMed
30.Kanfer, JN, Hattori, H, Oribel, D.Reduced phospholipase Dactivity in brain tissue samples from Alzheimer’s disease patients. Ann Neurol 1986; 20: 265–267.CrossRefGoogle Scholar
31.Barany, M, Chang, YC, Arus, C, et al. Increased glycerol-3-phos-phorylcholine in post-mortem Alzheimer’s brain. Lancet 1 1985; 517.CrossRefGoogle ScholarPubMed