Martin-Ruiz C, Court J, Lee M, Piggott M, Johnson M, Ballard C, Kalaria R, Perry R, Perry E
Joint MRC-Newcastle University Development in Clinical Brain Aging, Newcastle General Hospital, Newcastle upon Tyne, UK.
Acta Neurol Scand Suppl. 2000;176:34-41. doi: 10.1034/j.1600-0404.2000.00305.x.
Comparisons were made of nicotinic receptors in 3 major forms of dementia in old age. Although it is well established the involvement of nicotinic receptors in Alzheimer's disease (AD), their status in the other two main causes of dementia in old age-dementia with Lewy bodies (DLB) and vascular dementia (VaD) is not widely reported.
Temporal cortex was examined for epibatidine and alpha-bungarotoxin binding, and immunoreactivity of alpha4 and alpha7 nAChR subunits.
There were selective abnormalities in nicotinic receptor subtypes in the disorders examined. In AD there is a loss of high affinity receptor binding, reflecting a selective loss of alpha4 subunit, but no change in alpha7 subunits. Similar abnormalities in ligand binding are also apparent in DLB. In the VaD series, there was no overall loss of epibatidine binding or immunoreactivity for alpha4 or alpha7 subunits.
Loss of cortical receptor alpha4 subunit appears to be a characteristic feature of neurodegenerative dementia but not dementia of vascular origin. Since nicotinic receptors control cerebral vasodilation, the relative integrity of the receptors in VaD may auger well for nicotinic therapy in this disorder in which there is a cholinergic abnormality, to judge by the loss of the presynaptic enzyme.
