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Nicotinic receptors in dementia of Alzheimer, Lewy body and vascular types

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Objectives - 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. Methods – Temporal cortex was examined for epibatidine and α-bungarotoxin binding, and immunoreactivity of α4 and α7 nAChR subunits. Results – 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 α4 subunit, but no change in α7 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 α4 or α7 subunits. Conclusions – Loss of cortical receptor α4 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.

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Keywords: Alzheimer's disease; alpha 4 and alpha 7 nicotinic receptor subunits; cerebral cortex; dementia with Lewy bodies; vascular dementia

Document Type: Original Article

Affiliations: Joint MRC–Newcastle University Development in Clinical Brain Aging, Newcastle General Hospital, MRC Building, Newcastle upon Tyne, NE4 6BE, UK

Publication date: 2000-12-01

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