Selective nicotinic acetylcholine receptor subunit deficits identified in Alzheimer's disease, Parkinson's disease and dementia with Lewy bodies by immunoprecipitation

Antibodies raised against human α2-6 and β2-4 nicotinic receptor subunits were utilized to fractionate 3H-epibatidine binding in human temporal cortex and striatum. The predominant receptor subtypes in both regions contained α4 and β2 subunits. In normal cortex, 10% of binding was also associated with α2 subunits, whereas in the striatum, contributions by α6 (17%) and β3 (23%) were observed. Minimal binding (≤5%) was associated with α3.In Alzheimer's disease and dementia with Lewy bodies, cortical loss of binding was associated with reductions in α4 (50%, P < 0.01) and β2 (30–38%, P < 0.05). In Parkinson's disease and dementia with Lewy bodies, striatal deficits in α6 (91 and 59% respectively, P < 0.01) and β3 (72 and 75%, P < 0.05) tended to be greater than for α4 and β2 (50–58%, P < 0.05). This study demonstrates distinct combinations of subunits contributing to heteromeric nicotinic receptor binding in the human brain that are area/pathway specific and differentially affected by neurodegeneration.