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

Lookup NU author(s): Professor Ian McKeith

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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 alpha-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.


Publication metadata

Author(s): Mohamed NE, Howlett DR, Ma L, Francis PT, Aarsland D, Ballard CG, McKeith IG, Chen CP, Lai MKP

Publication type: Article

Publication status: Published

Journal: Journal of Neural Transmission

Year: 2014

Volume: 121

Issue: 1

Pages: 71-78

Print publication date: 12/07/2013

ISSN (print): 0300-9564

ISSN (electronic): 1435-1463

Publisher: Springer Wien

URL: http://dx.doi.org/10.1007/s00702-013-1067-0

DOI: 10.1007/s00702-013-1067-0


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Funding

Funder referenceFunder name
Norwegian Research Council
Western Norway Health Trust
UK NIHR Biomedical Research Unit on Lewy Body dementias award
NMRC/CG/NUHS/2010National Medical Research Council of Singapore
NMRC/CSA/032/2011National Medical Research Council of Singapore

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