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 alpha 2-6 and beta 2-4 nicotinic receptor subunits were utilized to fractionate H-3-epibatidine binding in human temporal cortex and striatum. The predominant receptor subtypes in both regions contained alpha 4 and beta 2 subunits. In normal cortex, 10% of binding was also associated with alpha 2 subunits, whereas in the striatum, contributions by alpha 6 (17%) and beta 3 (23%) were observed. Minimal binding (<= 5%) was associated with alpha 3. In Alzheimer's disease and dementia with Lewy bodies, cortical loss of binding was associated with reductions in alpha 4 (50%, P < 0.01) and beta 2 (30-38%, P < 0.05). in Parkinson's disease and dementia with Lewy bodies, striatal deficits in alpha 6 (91 and 59% respectively, P < 0.01) and beta 3 (72 and 75%, P < 0.05) tended to be greater than for alpha 4 and beta 2 (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