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

• Main Authors: Cecilia Gotti, Milena Moretti, Iwo Bohr, Iryna Ziabreva, Silvia Vailati, Renato Longhi, Loredana Riganti, Annalisa Gaimarri, Ian G. McKeith, Robert H. Perry, Dag Aarsland, Jan Petter Larsen, Emanuele Sher, Ruth Beattie, Francesco Clementi, Jennifer A. Court
• Format: Article
• Language: English
• Published: Elsevier 2006-08-01
• Series: Neurobiology of Disease
• Subjects: Nicotinic acetylcholine receptors; Subunits; Human brain; Alzheimer's disease; Parkinson's disease; Dementia with Lewy bodies
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996106000908

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.