Dementia with Lewy bodies and Parkinson’s disease dementia are different clinical phenotypes of Lewy body dementias (LBD) 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 (AMPA) 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 moderate losses of GluA2/3/4 immunoreactivities in LBD which correlated with higher predeath Hoehn & Yahr scores, a measure of motor disabilities; 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. Given recent proposals to use AMPA receptor antagonists in Parkinson’s disease, especially for levodopa-induced dyskinesia (Johnson et al. 2009), our data suggest both potential and caution in extending such therapeutic rationales to LBD in view of altered levels of receptor drug targets.

References

Mohamed NE, Howlett DR, Ma L, Francis PT, Aarsland D, Ballard CG, McKeith IG, Chen CP, Lai MK (This paper).

Johnson KA, Conn PJ, Niswender CM (2009) Glutamate receptors as therapeutic targets for Parkinson’s disease. CNS Neurol Disord Drug Targets 8:475-491.