Neurology and Preclinical Neurological Studies - Original Article

Journal of Neural Transmission

, Volume 121, Issue 1, pp 71-78

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

  • Nur-Ezan MohamedAffiliated withDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
  • , David R. HowlettAffiliated withWolfson Centre for Age-Related Diseases, King’s College London
  • , Lu MaAffiliated withDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
  • , Paul T. FrancisAffiliated withWolfson Centre for Age-Related Diseases, King’s College London
  • , Dag AarslandAffiliated withCentre for Age-Related Medicine, Stavanger University HospitalDepartment of Neurobiology, Care Sciences and Society, KI-Alzheimer Disease Research Centre, Karolinska Institute
  • , Clive G. BallardAffiliated withWolfson Centre for Age-Related Diseases, King’s College London
  • , Ian G. McKeithAffiliated withInstitute for Ageing and Health, Newcastle University
  • , Christopher P. ChenAffiliated withDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of SingaporeMemory, Aging and Cognition Centre, National University Health System
  • , Mitchell K. P. LaiAffiliated withDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of SingaporeMemory, Aging and Cognition Centre, National University Health SystemWolfson Centre for Age-Related Diseases, King’s College London Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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