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

Lookup NU author(s): Dr Iwo Bohr, Dr Iryna Ziabreva, Professor Ian McKeith, Emeritus Professor Robert Perry, Dr Dag Aarsland, Dr Jennifer Court

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Abstract

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. (c) 2006 Elsevier Inc. All rights reserved.


Publication metadata

Author(s): Gotti C, Moretti M, Bohr I, Ziabreva I, Vailati S, Longhi R, Riganti L, Gaimarri A, McKeith IG, Perry RH, Aarsland D, Larsen JP, Sher E, Beattie R, Clementi F, Court JA

Publication type: Article

Publication status: Published

Journal: Neurobiology of Disease

Year: 2006

Volume: 23

Issue: 2

Pages: 481-489

ISSN (print): 0969-9961

ISSN (electronic): 1095-953X

Publisher: Academic Press

URL: http://dx.doi.org/10.1016/j.nbd.2006.04.005

DOI: 10.1016/j.nbd.2006.04.005


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