Quantitative assessment of nicotinic acetylcholine receptor proteins in the cerebral cortex of Alzheimer patients.
Cholinergic transmission has for long been known to be one of the most severely affected systems in Alzheimer's disease (AD), resulting clinically in massive cognitive deficits. The molecular basis of this dysfunction--on both the pre- and the postsynaptic sites--is still a matter of ongoing investigations. Here, we report on the quantitative assessment of nicotinic acetylcholine receptor isoform expression in AD vs. control cortices. For both subunit proteins assessed, the alpha4 and the alpha7 isoform, highly significant decreases in diseased vs. normal cortices were observed. Both alpha4 and alpha7 subunits are known to be important constituents in hetero- (alpha4beta2) and homooligomeric (alpha7) receptor subtypes. Their decreased expression may contribute to the decreased nicotinic binding known to be accompanied by AD and severe cognitive deficits. The quantitative assessment of nicotinic acetylcholine receptor expression will help to determine those subunits suited as targets for pharmacological stimulation.
Burghaus
L
L
Department of Anatomy, University of Köln, J. Stelzmann-Strasse 9, D-50931, Cologne, Germany.
Schütz
U
U
Krempel
U
U
de Vos
R A
RA
Jansen Steur
E N
EN
Wevers
A
A
Lindstrom
J
J
Schröder
H
H
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000911:Antibodies, Monoclonal; D001344:Autopsy; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D020033:Protein Isoforms / Q000032:analysis; D011978:Receptors, Nicotinic / Q000032:analysis*
D000911:Antibodies, Monoclonal; D020033:Protein Isoforms; D011978:Receptors, Nicotinic