Nicotinic receptor abnormalities in Alzheimer's disease.
Loss of cortical nicotinic acetylcholine receptors with high affinity for agonists (20-50%) in patients with Alzheimer's disease is a common finding. Recent immunochemical analyses indicate that this deficit is predominantly associated with the loss of alpha4 subunits (30-50%), although modest reductions of alpha3 may occur in some individuals (25-29%). No reduction of beta2 subunit protein expression or levels of alpha3 and alpha4 messenger RNA has been reported. Decline in cortical [(125)I]alpha-bungarotoxin binding and alpha7 protein expression does not appear to be as extensive or widespread as the loss of alpha4 (0-40%), with no reduction in messenger RNA expression. In the thalamus, there was a trend for reduced [(3)H]nicotine binding in the majority of nuclei (0-20%) in Alzheimer's disease; however, there was a significant decline in [(125)I]alpha-bungarotoxin binding in the reticular nucleus. In the striatum [(3)H]nicotine binding was reduced in Alzheimer's disease, and although neuroleptic medication accentuated this change, it occurred in those free of neuroleptics. Changes in nicotinic acetylcholine receptors in Alzheimer's disease are distinct from those in normal aging and are likely to contribute to clinical features and possibly neuropathology.
Joint MRC Newcastle University Centre Development in Clinical Brain Aging, Institute for the Health of the Elderly, Newcastle General Hospital, Newcastle upon Tyne, United Kingdom.
J
J
Court
C
C
Martin-Ruiz
M
M
Piggott
D
D
Spurden
M
M
Griffiths
E
E
Perry
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology*; D001479:Basal Ganglia / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D011978:Receptors, Nicotinic / Q000145:classification / Q000502:physiology*; D013788:Thalamus / Q000473:pathology / Q000503:physiopathology
D011978:Receptors, Nicotinic