[en] There is a characteristic decrease in glucose metabolism in associative frontal and temporo-parietal cortices of patients suffering from Alzheimer's disease (AD). The decrease in metabolism might result from local neuronal loss or from a decrease of synaptic activity. We measured in vivo [11C]methionine accumulation into proteins with positron emission tomography (PET) to assess cortical tissue loss in AD. Both global regional activity and compartmental analysis were used to express [11C]methionine accumulation into brain tissue. Glucose metabolism was measures with [18F]fluorodeoxyglucose and autoradiographic method. Combined studies were performed in 10 patients with probable AD, compared to age-matched healthy volunteers. There was a significant 45% decrease of temporo-parietal glucose metabolism in patients with AD, and frontal metabolism was lowered in most patients. Temporo-parietal metabolism correlated to dementia severity. [11C]methionine incorporation into temporo-parietal and frontal cortices was not significantly decreased in AD. There was no correlation with clinical symptoms. Data suggest that regional tissue loss, assessed by the decrease of [11C]methionine accumulation, is not sufficient to explain cortical glucose hypometabolism, which reflects, rather, reduced synaptic connectivity.
Disciplines :
Neurosciences & behavior
Author, co-author :
Salmon, Eric ; Université de Liège - ULiège > Département des sciences cliniques > Neuroimagerie des troubles de la mémoire et révalid. cogn.
Grégoire, M. C.
Delfiore, Guy
Lemaire, Christian ; Université de Liège - ULiège > Centre de recherches du cyclotron
Degueldre, Christian ; Université de Liège - ULiège > Centre de recherches du cyclotron
Franck, Georges ; Université de Liège - ULiège > Relations académiques et scientifiques (Médecine)
Comar, D.
Language :
English
Title :
Combined study of cerebral glucose metabolism and [11C] methionine accumulation in probable Alzheimer's disease using positron emission tomography
American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders. 3rd ed, revised (DSM III-R). Washington, DC.
Antonini A, Vontobel P, Leenders KL (1995) Dynamic PET measurements of cerebral [18F]fluorodeoxyglucose brain transport and phosphorylation capacity in Alzheimer's disease [Abstract]. J Cereb Blood Flow Metab 15 (suppl 1):S786
Bagley PR, Tucker SP, Nolan C, Lindsay JG, Davies A, Baldwin SA, Cremer JE, Cunningham VJ (1989) Anatomical mapping of glucose transporter protein and pyruvate dehydrogenase in rat brain: an immunogold study. Brain Res 499:214-224
Bergström M, Ericson K, Hagenfeldt L, Mosskin M, von Holst H, Noren G, Eriksson L, Ehrin E, Johnström P (1987) PET study of methionine accumulation in glioma and normal brain tissue: competition with branched chain amino acids. J Comput Assist Tomogr 11:208-213
Blomqvist G (1993) Kinetic modelling of carbon-11 labelled amino acids. In: PET Studies on Amino Acid Metabolism and Protein Synthesis (Mazoyer BM, Heiss WD, Comar D, eds), Dordrecht: Kluwer Academic Publishers, pp 149-160
Bustany P, Henry JF, de Rotrou J, Signoret P, Cabanis E, Zarifian E, Ziegler M, Derlon M, Crouzel C, Soussaline F, Comar D (1985) Correlations between clinical state and positron emission tomography measurement of local brain protein synthesis in Alzheimer's dementia, Parkinson's disease. Schizophrenia and Gliomas. In: The Metabolism of the Human Brain Studied With Positron Emission Tomography (Greitz T, Ingvar DH, Widen L, eds). New York, Raven Press, pp 241-249
Chawluk JB, Alavi A, Dann R, Hurtig HI, Bais S, Kushner MJ, Zimmerman RA, Reivich M (1987) Positron emission tomography in aging and dementia: effect of cerebral atrophy. J Nucl Med 28:431-437
Clarke DD, Lajtha AL, Maker HS (1989) Intermediary metabolism. In: Basic Neurochemistry. 4th ed (Siegel G, Agranoff B, Albers RW, Molinoff P, eds), New York, Raven Press, pp 541-564
Comar D, Cartron SC, Maziere M, Marazano C (1976) Labelling and metabolism of methionine-methyl 11C. Eur J Nucl Med 1:11-14
Davies CA, Mann DM, Sumpter PQ, Yates PO (1987) A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer's disease. J Neurol Sci 78:151-164
Degueldre C, Quaglia L (1992) Performance evaluation of a new whole body positron tomograph: the ECAT 951/31 R. Proceedings of the 14th Annual International Conference of the IEEE Engineering in Medicine and Biology Society 1831-1833
DeKosky ST, Bass NH (1982) Aging, senile dementia, and the intralaminar microchemistry of cerebral cortex. Neurology 32:1227-1233
DeKosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer's disease; a correlation with cognitive severity. Ann Neurol 27:457-464
de Leon MJ, Ferris SH, George AE, Reisberg B, Christman DR, Kricheff II, Wolf AP (1983) Computed tomography and positron emission transaxial tomography evaluations of normal ageing and Alzheimer's disease. J Cereb Blood Flow Metab 3:391-394
Del Fiore G, Peters JM, Quaglia L, Boudjelida F, Pardon MC, Piette JL, Cantineau R, de Landsheere C, Rigo P (1986) Automated preparation of carbon-11 ethanol and carbon-11 butanol for human studies using positron emission tomography. J Radioanal Nucl Chem 104:301-316
Dick APK, Harik SI (1986) Distribution of the glucose transporter in the mammalian brain. J Neurochem 46:1406-1411
Duara R, Grady C, Haxby J, Sundaram M, Cutler NR, Heston L, Moore A, Schlageter N, Larson S, Rapoport SI (1986) Positron emission tomography in Alzheimer's disease. Neurology 36:879-887
Flood DG, Coleman PD (1986) Failed compensatory dendritic growth as a pathophysiological process in Alzheimer's disease. Can J Neurol Sci 13:475-479
Folstein M, Folstein SE, McHugh PR (1975) "Mini Mental State." A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189-198
Foster NL, Chase TN, Mansi L, Brooks R, Fedio P, Patronas NJ, Di Chiro G (1984) Cortical abnormalities in Alzheimer's disease. Ann Neural 16:649-654
Friedland RP, Jagust WJ, Huesman RH, Koss E, Knittel B, Mathis CA, Ober BA, Mazoyer BM, Budinger TF (1989) Regional cerebral glucose transport and utilisation in Alzheimer's disease. Neurology 39:1427-1434
Fukuyama H, Kameyama M, Harada K, Nishizawa S, Senda M, Mukai T, Yonekura Y, Torizuka K (1989) Glucose metabolism and rate constants in Alzheimer's disease examined with dynamic PET scan. Acta Neurol Scand 80:307-313
Grange E, Gharib A, Lepetit P, Guillaud J, Sarda N, Bobillier P (1992) Brain protein synthesis in the conscious rat using L-[35S]methionine: relationship of methionine specific activity between plasma and precursor compartment and evaluation of methionine metabolic pathways. J Neurochem 59: 1437-1443
Hamacher K, Coenen HH, Stöcklin G (1986) Efficient stereo-specific synthesis of no-carrier-added 2-[18F]-fluoro-2-deoxy-D-glucose using aminopolyether supported nucleophilic substitution. J Nucl Med 27:235-238
Hamberger A, Blomstrand C, Yanagihara T (1971) Subcellular distribution of radioactivity in neuronal and glial-enriched fractions after incorporation of [3H]leucine in vivo and in vitro. J Neurochem 18:1469-1478
Hamberger A, Sourander P (1978) The influence of early protein-caloric malnutrition on neuronal and glial protein synthesis. An experimental study on rats. Neurochem Res 3:535-547
Hammersschlag R, Brady ST (1989) Axonal transport and the neuronal cytoskeleton. In: Basic Neurochemistry: Molecular, Cellular, and Medical Aspects, 4th ed (Siegel G, Agranoff B, Albers RW, Molinoff P, eds), New York, Raven Press, pp 457-478
Hamos JE, DeGennaro LJ, Drachman DA (1989) Synaptic loss in Alzheimer's disease and other dementias. Neurology 39: 355-361
Hansen LA, DeTeresaR, Davies P, Terry RD(1988) Neocortical morphometry, lesion counts, and choline acetyltransferase levels in the age spectrum of Alzheimer's disease. Neurology 38:48-54
Haxby JV, Duara R, Grady CL, Cutler NR, Rapoport SI (1985) Relations between neuropsychological and cerebral metabolic asymmetries in early Alzheimer's disease. J Cereb Blood Flow Metab 5:193-200
Haxby JV, Grady CL, Duara R, Schlageter N, Berg G, Rapoport SI (1986) Neocortical metabolic abnormalities precede nonmemory cognitive defects in early Alzheimer's type dementia. Arch Neurol 43:882-885
Herholz K, Perani D, Salmon E, Franck G, Fazio F, Heiss WD, Comar D (1993) Comparability of FDG PET studies in probable Alzheimer's disease. J Nucl Med 34:1460-1466
Herscovitch P, Auchus AP, Gado M, Chi D, Raichle ME (1986) Correction of positron emission tomography data for cerebral atrophy. J Cereb Blood Flow Metab 6:120-124
Ishiwata K, Hatazawa J, Kubota K, Kameyama M, Itoh M, Matsuzawa T, Takahashi T, Iwata R, Ido T (1989) Metabolic fate of L-[methyl-11C]methionine in human plasma. Eur J Nucl Med 15:665-669
Jagust WJ, Scab JP, Huesman RH, Valk PE, Mathis CA, Reed BR, Coxson PG, Budinger T (1991) Diminished glucose transport in Alzheimer's disease: dynamic PET studies. J Cereb Blood Flow Metab 11:323-330
Kuhl DE, Metter EJ, Riege WH (1985) Patterns of cerebral glucose utilisation in depression, multiple infarct dementia, and Alzheimer's disease. In: Brain Imaging and Brain Function (Sokoloff L, ed). New York, Raven Press, pp 211-226
Lajtha A, Dunlop D, Banay-Schwartz M (1993) Cerebral protein turnover: aspects and problems. In: PET Studies on Amino Acid Metabolism and Protein Synthesis (Mazoyer BM, Heiss WD, Comar D, eds), Dordrecht, Kluwer Academic Publishers, pp 1-17
Lajtha A, Dunlop D (1981) Turnover of protein in the nervous system. Life Sci 29:755-767
Lajtha A, Latzkovits L, Toth J (1976) Comparison of turnover rates of proteins of the brain, liver, and kidney in mouse in vivo following long term labelling. Biochem Biophys Acta 425:511-520
Lestage P, Gonon M, Lepetit P, Vine PA, Debilly G, Rossatto C, Lecestre D, Bobillier P (1987) An in vivo kinetic model with L-[35S]methionine for the determination of local cerebral rates for methionine incorporation into protein in the rat. J Neurochem 48:352-363
Lukiw WJ, Handley P, Sutherland MK, Wong L, McLachlan DR (1991) A correlation between gene transcriplional activity and cerebral glucose metabolism in Alzheimer's disease-affected neocortex. Adv Exp Med Biol 291:249-256
Mann DMA, Marcyniuk B, Yates PO, Neary D, Snowden JS (1988) The progression of the pathological changes of Alzheimer's disease in frontal and temporal neocortex examined both at biopsy and at autopsy. Neuropathol Appl Neurobiol 14:177-195
McGeer PL, Kamo H, Harrop R, McGeer EG, Martin WRW, Pate BD, Li DKB (1986) Comparison of PET, MRI, and CT with pathology in a proven case of Alzheimer's disease. Neurology 36:1569-1574
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer's disease. Neurology 34:939-944
Messa C, Perani D, Lucignani G, et al (1994) High-resolution technetium-99m-HMPAO SPECT in patients with probable Alzheimer's disease: comparison with fluorine-18-FDG PET. J Nucl Med 35:210-216
Najlerahim A, Bowen DM (1988) Biochemical measurements in Alzheimer's disease reveal a necessity for improved neuroimaging techniques to study metabolism. Biochem J 251: 305-308
Neary D, Snowden JS, Mann DMA, Bowen DM, Sims NR, Northen B, Yates PO, Davison AN (1986) Alzheimer's disease: a correlative study. J Neurol Neurosurg Psychiatry 49:229-237
O'Tuama LA, Guilarte TR, Douglass KH, Wagner HN, Wong DF, Dannals RF, Ravert HT, Wilson AA, LaFrance ND, Bice AN, Links JM (1988) Assessment of [11C]-L-methionine transport into the human brain. J Cereb Blood Flow Metab 8:341-345
Phelps ME, Barrio JR, Huang SC, Keen RE, Chugani H, Mazziotta JC (1984) Criteria for the tracer kinetic measurement of cerebral protein synthesis in humans with positron emission tomography. Ann Neurol 15:S192-S202
Phelps ME, Huang SE, Huffman EJ, Selin SC, Sokoloff L, Kuhl DE (1979) Tomographic measurement of local cerebral metabolic rate in humans with (F-18) 2-fluoro-2-deoxyglucose: validation of method. Ann Neurol 6:371-388
Planas AM, Prenant C, Mazoyer BM, Comar D, DiGiamberardino L (1992) Regional cerebral L-[14C-methyl]methionine incorporation into proteins: evidence for methionine recycling in the rat brain. J Cereb Blood Flow Metab 12:603-612
Procter AW, Lowe SL, Palmer AM, Francis PT, Esiri MM, Stratmann GC, Nallerahim A, Patel AJ, Hunt A, Bowen DM (1988) Topographical distribution of neurochemical changes in Alzheimer's disease. J Neurol Sci 84:125-140
Reisert I, Pilgrim Ch, Venedey Ch. Incorporation of (3H)leucine into hypothalamic nerve and glial cells (1979) A comparison by EM autoradiography. Brain Res 172:521-532
Salmon E, Sadzot B, Maquet P, Degueldre Chr, Lemaire Chr, Rigo P, Comar D, Franck G (1994) Differential diagnosis of Alzheimer's disease with positron emission tomography. J Nucl Med 35:391-398
Sato K, Kameyama M, Ishiwata K, Hatazawa J, Katakura R, Yoshimoto T (1992) Dynamic study of methionine uptake in glioma using positron emission tomography. Eur J Nucl Med 19:426-430
Schechter R, Yen SH, Terry RD (1981) Fibrous astrocytes in senile dementia of the Alzheimer type. J Neuropath Exp Neurol 40:95-101
Schlageter NL, Horwitz B, Creasy H, Carson R, Duara R, Berg GW, Rapoport SI (1987) Relation of measured brain glucose utilisation and cerebral atrophy in man. J Neurol Neurosurg Psychiatry 50:779-785
Shahbazian FM, Jacobs M, Lajtha A (1986) Regional and cellular differences in rat brain protein synthesis in vivo and in slices during development. Int J Devel Neurosci 4:209-215
Smith GS, de Leon M, George AE, Kluger A, Volkow ND, McRae T, Golomb J, Ferris SH, Reisberg B, Ciaravino J, La Regina ME (1992) Topography of cross-sectional and longitudinal glucose metabolic deficits in Alzheimer's disease. Arch Neurol 49:1142-1150
Tomlinson BE, Corsellis JAN (1984) Ageing and the dementia. In: Greenfield's Neuropathology, 4th ed (Hume Adams J, Corsellis JAN, Duchen LW, eds), London, Edward Arnold, pp 951-1025
Vaalburg W, Elsinga PH, Paans AMJ (1993) Carbon-11 amino acids, labelling and metabolites. In: PET Studies on Amino Acid Metabolism and Protein Synthesis (Mazoyer BM, Heiss WD, Comar D, eds), Dordrecht, Kluwer Academic Publishers, pp 75-80
