Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy body diseases

Human brain ageing is associated with reductions in a variety of nicotinic receptors subtypes, whereas changes in age-related disorders including Alzheimer's disease or Parkinson's disease are more selective. In Alzheimer's disease, in the cortex there is a selective loss of the alpha 4 (but not alpha 3 or 7) subunit immunoreactivity and of nicotine or epibatidine binding but not a-bungarotoxin binding. Epibatidine binding is inversely correlated with clinical dementia ratings and with the level of A beta 1-42, but not related to plaque or tangle densities in contrast, alpha-bungarotoxin binding is positively correlated with plaque densities in the entorhinal cortex. In human temporal cortex loss of acetylcholinesterase catalytic activity is positively correlated with decreased epibatidine binding and in a transgenic mouse model over expressing acetylcholinesterase, epibatidine binding is elevated. In Parkinson's disease, loss of striatal nicotine binding appears to occur early but is not associated with a loss of alpha 4 subunit immunoreactivity. Tobacco use in normal elderly individuals is associated with increased alpha 4 immunoreactivity in the cortex and lower densities of amyloid-beta plaques, and with greater numbers of dopaminergic neurons in the substantia nigra pars compacta. These findings indicate an early involvement of the alpha 4 subunit in beta-amyloidosis but not in nigro-striatal dopaminergic degeneration. (C) 2000 Elsevier Science B.V. All rights reserved.