title: Decreased immunoreactivities of neocortical AMPA receptor subunits correlate with motor disability in Lewy body dementias.
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.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore, 117597, Singapore.
authors.forename: Nur-Ezan
authors.initials: NE
authors.lastname: Mohamed
authors.forename: David R
authors.initials: DR
authors.lastname: Howlett
authors.forename: Lu
authors.initials: L
authors.lastname: Ma
authors.forename: Paul T
authors.initials: PT
authors.lastname: Francis
authors.forename: Dag
authors.initials: D
authors.lastname: Aarsland
authors.forename: Clive G
authors.initials: CG
authors.lastname: Ballard
authors.forename: Ian G
authors.initials: IG
authors.lastname: McKeith
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Chen
authors.forename: Mitchell K P
authors.initials: MK
authors.lastname: Lai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009048:Motor Skills / Q000502:physiology*; D019579:Neocortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D021122:Protein Subunits / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D021122:Protein Subunits; D018091:Receptors, AMPA