Journal of Neural Transmission

, Volume 121, Issue 1, pp 71–78 | Cite as

Decreased immunoreactivities of neocortical AMPA receptor subunits correlate with motor disability in Lewy body dementias

  • Nur-Ezan Mohamed
  • David R. Howlett
  • Lu Ma
  • Paul T. Francis
  • Dag Aarsland
  • Clive G. Ballard
  • Ian G. McKeith
  • Christopher P. Chen
  • Mitchell K. P. Lai
Neurology and Preclinical Neurological Studies - Original Article

Abstract

Dementia with Lewy bodies and Parkinson’s disease dementia are different clinical phenotypes of Lewy body dementias differentiated by the temporal relationship between parkinsonism and dementia onset. At present, it is unclear whether the glutamatergic system is affected in these disorders. In this study, we measured α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor GluA subunits in the postmortem neocortex of a cohort of prospectively studied Lewy body dementia cases, as well as age-matched controls by immunoblotting. We found losses of GluA2/3/4 immunoreactivities in Lewy body dementias which correlated with higher pre-death Hoehn and Yahr scores and with longer Parkinson’s disease duration before dementia onset, but not with dementia severity, cortical Lewy body burden, or amyloid plaque and neurofibrillary tangle burden. Our study suggests that GluA2/3/4 losses may be a neurochemical marker of motor disability in Lewy body dementias.

Keywords

AMPA receptors Lewy body dementia Neocortex Motor function Glutamatergic system 

Supplementary material

702_2013_1067_MOESM1_ESM.pdf (103 kb)
Supplementary material 1 (PDF 103 kb)

References

  1. Aarsland D, Tandberg E, Larsen JP, Cummings JL (1996) Frequency of dementia in Parkinson disease. Arch Neurol 53:538–542PubMedCrossRefGoogle Scholar
  2. Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sorensen P (2003) Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol 60:387–392PubMedCrossRefGoogle Scholar
  3. Aarsland D, Londos E, Ballard C (2009) Parkinson’s disease dementia and dementia with Lewy bodies: different aspects of one entity. Int Psychogeriatr 21:216–219PubMedCrossRefGoogle Scholar
  4. Ballard C, O’Brien J, Gray A et al (2001a) Attention and fluctuating attention in patients with dementia with Lewy bodies and Alzheimer disease. Arch Neurol 58:977–982PubMedCrossRefGoogle Scholar
  5. Ballard C, Walker M, O’Brien J, Rowan E, McKeith I (2001b) The characterisation and impact of ‘fluctuating’ cognition in dementia with Lewy bodies and Alzheimer’s disease. Int J Geriatr Psychiatry 16:494–498CrossRefGoogle Scholar
  6. Ballard C, Ziabreva I, Perry R et al (2006) Differences in neuropathologic characteristics across the Lewy body dementia spectrum. Neurology 67:1931–1934PubMedCrossRefGoogle Scholar
  7. Boeve BF, Silber MH, Parisi JE et al (2003) Synucleinopathy pathology and REM sleep behavior disorder plus dementia or parkinsonism. Neurology 61:40–45PubMedCrossRefGoogle Scholar
  8. Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol (Berl) 82:239–259CrossRefGoogle Scholar
  9. Calabresi P, Centonze D, Bernardi G (2000) Electrophysiology of dopamine in normal and denervated striatal neurons. Trends Neurosci 23:S57–S63CrossRefGoogle Scholar
  10. Campbell K, Bjorklund A (1994) Prefrontal corticostriatal afferents maintain increased enkephalin gene expression in the dopamine-denervated rat striatum. Eur J Neurosci 6:1371–1383PubMedCrossRefGoogle Scholar
  11. Carlsson M, Carlsson A (1990) Interactions between glutamatergic and monoaminergic systems within the basal ganglia––implications for schizophrenia and Parkinson’s disease. Trends Neurosci 13:272–276PubMedCrossRefGoogle Scholar
  12. Carter TL, Rissman RA, Mishizen-Eberz AJ (2004) Differential preservation of AMPA receptor subunits in the hippocampi of Alzheimer’s disease patients according to Braak stage. Exp Neurol 187:299–309PubMedCrossRefGoogle Scholar
  13. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198CrossRefGoogle Scholar
  14. Francis PT, Ramírez MJ, Lai MK (2010) Neurochemical basis for symptomatic treatment of Alzheimer’s disease. Neuropharmacology 59:221–229PubMedCrossRefGoogle Scholar
  15. Gainetdinov RR, Mohn AR, Bohn LM, Caron MG (2001) Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter. Proc Natl Acad Sci USA 98:11047–11054PubMedCrossRefGoogle Scholar
  16. Gelb DJ, Oliver E, Gilman S (1999) Diagnostic criteria for Parkinson disease. Arch Neurol 56:33–39PubMedCrossRefGoogle Scholar
  17. Goetz CG, Poewe W, Rascol O et al (2004) Movement disorder society task force report on the Hoehn and Yahr staging scale: status and recommendations. Mov Disord 19:1020–1028PubMedCrossRefGoogle Scholar
  18. Goetz CG, Fahn S, Martinez-Martin P et al (2007) Movement disorder society-sponsored revision of the unified Parkinson’s disease rating scale (MDS-UPDRS): process, format, and clinic metric testing plan. Mov Disord 22:41–47PubMedCrossRefGoogle Scholar
  19. Gong Y, Lippa CF, Zhu J, Lin Q, Rosso AL (2009) Disruption of glutamate receptors at shank-postsynaptic platform in Alzheimer’s disease. Brain Res 1292:191–198PubMedCentralPubMedCrossRefGoogle Scholar
  20. Griffith HR, den Hollander JA, Okonkwo OC, O’Brien T, Watts RL, Marson DC (2008a) Brain metabolism differs in Alzheimer’s disease and Parkinson’s disease dementia. Alzheimers Dement 4:421–427PubMedCentralPubMedCrossRefGoogle Scholar
  21. Griffith HR, Okonkwo OC, O’Brien T, Hollander JA (2008b) Reduced brain glutamate in patients with Parkinson’s disease. NMR Biomed 21:381–387PubMedCrossRefGoogle Scholar
  22. Isaac JT, Ashby M, McBain CJ (2007) The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity. Neuron 54:859–871PubMedCrossRefGoogle Scholar
  23. Jellinger KA (2009) Significance of brain lesions in Parkinson disease dementia and Lewy body dementia. Fron Neurol Neurosci 24:114–125CrossRefGoogle Scholar
  24. Johnson KA, Conn PJ, Niswender CM (2009) Glutamate receptors as therapeutic targets for Parkinson’s disease. CNS Neurol Disord: Drug Targets 8:475–491CrossRefGoogle Scholar
  25. Kalaria RN, Kenny RA, Ballard CG, Perry R, Ince P, Polvikoski T (2004) Towards defining the neuropathological substrates of vascular dementia. J Neurol Sci 226:75–80PubMedCrossRefGoogle Scholar
  26. Kim DY, Kim SH, Choi HB, Min C, Gwag BJ (2001) High abundance of GluR1 mRNA and reduced Q/R editing of GluR2 mRNA in individual NADPH-diaphorase neurons. Mol Cell Neurosci 17:1025–1033PubMedCrossRefGoogle Scholar
  27. Lindefors N, Ungerstedt U (1990) Bilateral regulation of glutamate tissue and extracellular levels in caudate–putamen by midbrain dopamine neurons. Neurosci Lett 115:248–252PubMedCrossRefGoogle Scholar
  28. Malinow R, Malenka RC (2002) AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci 25:103–126PubMedCrossRefGoogle Scholar
  29. McKeith IG, Galasko D, Kosaka K et al (1996) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 47:1113–1124PubMedCrossRefGoogle Scholar
  30. McKeith IG, Dickson DW, Lowe J et al (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65:1863–1872PubMedCrossRefGoogle Scholar
  31. Mirra SS, Heyman A, McKeel D et al (1991) The consortium to establish a registry for Alzheimer’s disease (CERAD) part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41:479–486PubMedCrossRefGoogle Scholar
  32. Modrego PJ, Fayed N, Artal J, Olmos S (2011) Correlation of findings in advanced MRI techniques with global severity scales in patients with Parkinson disease. Acad Radiol 18:235–241PubMedCrossRefGoogle Scholar
  33. Mohamed NE, Zhao Y, Lee JH et al (2011) Upregulation of AMPA receptor GluR2 (GluA2) subunits in subcortical ischemic vascular dementia is repressed in the presence of Alzheimer’s disease. Neurochem Int 58:820–825PubMedCrossRefGoogle Scholar
  34. Monoranu CM, Apfelbacher M, Grunblatt E et al (2009) pH measurement as quality control on human post mortem brain tissue: a study of the brain net Europe consortium. Neuropathol Appl Neurobiol 35:329–337PubMedCrossRefGoogle Scholar
  35. Reid WA, Valler MJ, Kay J (1986) Immunolocalization of cathepsin D in normal and neoplastic human tissues. J Clin Pathol 39:1323–1330PubMedCrossRefGoogle Scholar
  36. Sgambato-Faure V, Cenci MA (2012) Glutamatergic mechanisms in the dyskinesias induced by pharmacological dopamine replacement and deep brain stimulation for the treatment of Parkinson’s disease. Prog Neurobiol 96:69–86PubMedCrossRefGoogle Scholar
  37. Strafella AP, Ko JH, Grant J, Fraraccio M, Monchi O (2005) Corticostriatal functional interactions in Parkinson’s disease: a rTMS/[11C]raclopride PET study. Eur J Neurosci 22:2946–2952PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Nur-Ezan Mohamed
    • 1
  • David R. Howlett
    • 3
  • Lu Ma
    • 1
  • Paul T. Francis
    • 3
  • Dag Aarsland
    • 4
    • 5
  • Clive G. Ballard
    • 3
  • Ian G. McKeith
    • 6
  • Christopher P. Chen
    • 1
    • 2
  • Mitchell K. P. Lai
    • 1
    • 2
    • 3
  1. 1.Department of Pharmacology, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
  2. 2.Memory, Aging and Cognition CentreNational University Health SystemSingaporeSingapore
  3. 3.Wolfson Centre for Age-Related DiseasesKing’s College LondonLondonUK
  4. 4.Centre for Age-Related MedicineStavanger University HospitalStavangerNorway
  5. 5.Department of Neurobiology, Care Sciences and Society, KI-Alzheimer Disease Research CentreKarolinska InstituteStockholmSweden
  6. 6.Institute for Ageing and HealthNewcastle UniversityNewcastle upon TyneUK

Personalised recommendations