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Serum Glutamine Synthetase Has No Value as a Diagnostic Biomarker for Alzheimer’s Disease

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Abstract

In order to test whether serum glutamine synthetase (GS) is of potential diagnostic value for Alzheimer’s disease (AD), we set up a study to compare serum GS concentrations between AD patients and control subjects. The study population (n = 165) consisted of AD patients (n = 94) and age-matched (n = 41) and age-unmatched (n = 30) control subjects. Serum GS analysis was performed by means of ELISA. No significant differences in serum GS levels were found between the AD group and age-matched controls. Age correlated positively with serum GS concentrations in AD patients and control subjects. This study suggests that serum GS levels have no diagnostic value for AD.

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References

  1. Meister A (1974) Glutamine synthetase of mammals. In: Boyer PD (ed) The enzymes, vol 10. Academic Press, New York, pp 699–754

    Google Scholar 

  2. Suárez I, Bodega G, Fernández B (2002) Glutamine synthetase in brain: effect of ammonia. Neurochem Int 41:123–142

    Article  PubMed  Google Scholar 

  3. Finch CE, Cohen DM (1997) Aging, metabolism, and Alzheimer disease: review and hypotheses. Exp Neurol 143:82–102

    Article  PubMed  CAS  Google Scholar 

  4. Smith CD, Carney JM, Starke-Reed PE et al (1991) Excess brain protein oxidation and enzyme dysfunction in normal aging and Alzheimer disease. Proc Natl Acad Sci USA 88:10540–10543

    Article  PubMed  CAS  Google Scholar 

  5. Le Prince G, Delaere P, Fages C et al (1995) Glutamine synthetase (GS) expression is reduced in senile dementia of the Alzheimer type. Neurochem Res 20:859–862

    Article  PubMed  CAS  Google Scholar 

  6. Aksenov MY, Aksenova MV, Harris ME et al (1995) Enhancement of beta-amyloid A beta(1–40)-mediated neurotoxicity by glutamine synthetase. J Neurochem 65:1899–1902

    Article  PubMed  CAS  Google Scholar 

  7. Aksenov MY, Aksenova MV, Butterfield DA et al (1996) Glutamine synthetase-induced enhancement of beta-amyloid peptide A beta(1–40) neurotoxicity accompanied by abrogation of fibril formation and A beta fragmentation. J Neurochem 66:2050–2056

    Article  PubMed  CAS  Google Scholar 

  8. Aksenov MY, Aksenova MV, Carney JM et al (1997) Oxidative modification of glutamine synthetase by amyloid beta peptide. Free Radic Res 27:267–281

    Article  PubMed  CAS  Google Scholar 

  9. Varadarajan S, Yatin S, Aksenova M et al (2000) Review: Alzheimer’s amyloid β-peptide-associated free radical oxidative stress and neurotoxicity. J Struct Biol 130:184–208

    Article  PubMed  CAS  Google Scholar 

  10. Poon HF, Joshi G, Sultana R et al (2004) Antisense directed at the Abeta region of APP decreases brain oxidative markers in aged senescence accelerated mice. Brain Res 1018:86–96

    Article  PubMed  CAS  Google Scholar 

  11. Sato E, Oda N, Ozaki N et al (1996) Early and transient increase in oxidative stress in the cerebral cortex of senescence-accelerated mouse. Mech Ageing Dev 86:105–114

    Article  PubMed  CAS  Google Scholar 

  12. Contestabile A, Fila T, Bartesaghi R et al (2006) Choline acetyltransferase activity at different ages in brain of Ts65Dn mice, an animal model for Down’s syndrome and related neurodegenerative diseases. J Neurochem 97:515–526

    Article  PubMed  CAS  Google Scholar 

  13. Butterfield DA, Hensley K, Cole P et al (1997) Oxidatively induced structural alteration of glutamine synthetase assessed by analysis of spin label incorporation kinetics: relevance to Alzheimer’s disease. J Neurochem 68:2451–2457

    Article  PubMed  CAS  Google Scholar 

  14. Gunnersen D, Haley B (1992) Detection of glutamine synthetase in the cerebrospinal fluid of Alzheimer diseased patients: a potential diagnostic biochemical marker. Biochemistry 89:11949–11953

    CAS  Google Scholar 

  15. Tumani H, Shen G, Peter JB et al (1999) Glutamine synthetase in cerebrospinal fluid, serum, and brain. Arch Neurol 56:1241–1246

    Article  PubMed  CAS  Google Scholar 

  16. Takahashi M, Stanton E, Moreno JI et al (2002) Immunoassay for serum glutamine synthetase in serum: development, reference values, and preliminary study in dementias. Clin Chem 48:375–378

    PubMed  CAS  Google Scholar 

  17. Burbaeva GS, Boksha IS, Tereshkina EB et al (2005) Glutamate metabolizing enzymes in prefrontal cortex of Alzheimer’s disease patients. Neurochem Res 30:1443–1451

    Article  PubMed  CAS  Google Scholar 

  18. Robinson SR (2001) Changes in the cellular distribution of glutamine synthetase in Alzheimer’s disease. J Neurosci Res 66:972–980

    Article  PubMed  CAS  Google Scholar 

  19. Kish S, Chang L, Dixon L et al (1994) Cerebellar glutamate metabolizing enzymes in spinocerebellar ataxia type I. Metab Brain Dis 9:97–103

    Article  PubMed  CAS  Google Scholar 

  20. Lavoie J, Giguere J, Layrargues G et al (1987) Activities of neuronal and astrocytic marker enzymes in autopsied brain tissue from patients with hepatic encephalopathy. Metab Brain Dis 2:283–290

    Article  PubMed  CAS  Google Scholar 

  21. Aluise CD, Sowell RA, Butterfield DA (2008) Peptides and proteins in plasma and cerebrospinal fluid as biomarkers for the prediction, diagnosis, and monitoring of therapeutic efficacy of Alzheimer’s disease. Biochm Biophys Acta 1782:549–558

    CAS  Google Scholar 

  22. Le Bastard N, Aerts L, Leurs J et al (2009) No correlation between time-linked plasma and CSF Aβ levels. Neurochem Int 55:820–825

    Article  PubMed  CAS  Google Scholar 

  23. Le Bastard N, Leurs J, Blomme W et al (2010) Plasma amyloid-beta forms in Alzheimer’s disease and non-Alzheimer’s disease patients. J Alzheimers Dis 21:291–301

    PubMed  CAS  Google Scholar 

  24. Schneider P, Hampel H, Buerger K (2009) Biological marker candidates of Alzheimer’s disease in blood, plasma, and serum. CNS Neurosci Ther 15:358–374

    Article  PubMed  CAS  Google Scholar 

  25. McKhann G, Drachman D, Folstein M et al (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

    PubMed  CAS  Google Scholar 

  26. American Psychiatric Association (1994) DSM-IV: diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington

    Google Scholar 

  27. Román GC, Tatemichi TK, Erkinjuntti T et al (1993) Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN international workshop. Neurology 43:250–260

    PubMed  Google Scholar 

  28. Folstein M, Folstein S, McHugh PR (1975) Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–196

    Article  PubMed  CAS  Google Scholar 

  29. Engelborghs S, Sleegers K, Cras P et al (2007) No association of CSF biomarkers with APOEε4, plaque and tangle burden in definite Alzheimer’s disease. Brain 130:2320–2326

    Article  PubMed  Google Scholar 

  30. Andreasen N, Blennow K (2005) CSF biomarkers for mild cognitive impairment and early Alzheimer’s disease. Clin Neurol Neurosurg 107:165–173

    Article  PubMed  Google Scholar 

  31. Fei M, Jianghua W, Rujuan M et al. (2011) The relationship of plasma Aβ levels to dementia in aging individuals with mild cognitive impairment. J Neurol Sci doi:10.1016/j.jns.2011.03.005

  32. Danh C, Benedetti S, Dostert P (1985) Age-related changes in glutamine synthetase activity of rat brain, liver and heart. Gerontology 31:95–100

    Article  Google Scholar 

  33. Launer LJ, Andersen K, Dewey ME et al (1999) Rates and risk factors for dementia and Alzheimer’s disease: results from EURODEM pooled analyses. EURODEM incidence research group and work groups. European studies of dementia. Neurology 52:78–84

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by the Special Research Fund of the University of Antwerp; Stichting Alzheimer Onderzoek; the Thomas Riellaerts Research Fund; the Institute Born-Bunge; the agreement between the Institute Born-Bunge and the University of Antwerp; the central Biobank facility of the Institute Born-Bunge/University of Antwerp; Neurosearch Antwerp; the Fund for Scientific Research - Flanders (FWO-F); the Interuniversity Attraction Poles (IAP) program P6/43 of the Belgian Federal Science Policy Office; the Methusalem excellence grant of the Flemish Government, Belgium. NLB is a PhD fellow of the Research Foundation - Flanders (FWO-F). The authors acknowledge the technical assistance of E. De Leenheir, G. Van de Vijver, F. Franck and J. Luyckx, the administrative assistance of S. Hicketick, W. Wittebolle, and A. Eykens, and the clinical staff involved.

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Authors and Affiliations

  1. Laboratory of Neurochemistry and Behavior, Reference Center for Biological Markers of Memory Disorders, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Wilrijk, Belgium

    Yannick Vermeiren, Nathalie Le Bastard, Sebastiaan Engelborghs & Peter P. De Deyn

  2. Biobank, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium

    Peter P. De Deyn

  3. Department of Neurology and Memory Clinic, Middelheim and Hoge Beuken General Hospitals (ZNA), Lindendreef 1, 2020, Antwerp, Belgium

    Sebastiaan Engelborghs & Peter P. De Deyn

  4. Department of Health Care Science, Artesis University College of Antwerp, J. De Boeckstraat 10, 2170, Merksem, Belgium

    Sebastiaan Engelborghs & Peter P. De Deyn

  5. Department of Nursing Sciences, Faculty of Medicine, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium

    Sebastiaan Engelborghs

  6. Department of Neurology and Alzheimer’s Disease Center, University of Pennsylvania, 3615 Chestnut St, Philadelphia, PA, 19104, USA

    Christopher M. Clark

Authors
  1. Yannick Vermeiren
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  2. Nathalie Le Bastard
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  3. Christopher M. Clark
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  4. Sebastiaan Engelborghs
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  5. Peter P. De Deyn
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Correspondence to Peter P. De Deyn.

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Vermeiren, Y., Le Bastard, N., Clark, C.M. et al. Serum Glutamine Synthetase Has No Value as a Diagnostic Biomarker for Alzheimer’s Disease. Neurochem Res 36, 1858–1862 (2011). https://doi.org/10.1007/s11064-011-0504-4

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  • DOI: https://doi.org/10.1007/s11064-011-0504-4

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