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 a2-6 and b2-4 nicotinic receptor subunits were utilized to fractionate 3H-epibatidine binding in human temporal cortex and striatum. The predominant receptor subtypes in both regions contained a4 and b2 subunits. In normal cortex, 10% of binding was also assocd. with a2 subunits, whereas in the striatum, contributions by a6 (17%) and b3 (23%) were obsd. Minimal binding (?5%) was assocd. with a3. In Alzheimer's disease and dementia with Lewy bodies, cortical loss of binding was assocd. with redns. in a4 (50%, P < 0.01) and b2 (30-38%, P < 0.05). In Parkinson's disease and dementia with Lewy bodies, striatal deficits in a6 (91 and 59% resp., P < 0.01) and b3 (72 and 75%, P < 0.05) tended to be greater than for a4 and b2 (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. [on SciFinder (R)]