Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy bodydiseases

Human brain ageing is associated with reductions in a variety of nicotinic receptors subtypes, whereas changes in age-related disorders including Alzh eimer's disease or Parkinson's disease are more selective. In Alzheimer's d isease, in the cortex there is a selective loss of the alpha 4 (but not alp ha 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 bindi ng is positively correlated with plaque densities in the entorhinal cortex. In human temporal cortex loss of acetylcholinesterase catalytic activity i s positively correlated with decreased epibatidine binding and in a transge nic mouse model over expressing acetylcholinesterase, epibatidine binding i s elevated. In Parkinson's disease, loss of striatal nicotine binding appea rs to occur early but is not associated with a loss of alpha 4 subunit immu noreactivity. Tobacco use in normal elderly individuals is associated with increased alpha 4 immunoreactivity in the cortex and lower densities of amy loid-beta plaques, and with greater numbers of dopaminergic neurons in the substantia nigra pars compacta. These findings indicate an early involvemen t of the alpha 4 subunit in beta-amyloidosis but not in nigro-striatal dopa minergic degeneration. (C) 2000 Elsevier Science B.V. All rights reserved.