Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Perry, E. et al.

Perry, Martin-Ruiz, Lee, Griffiths, Johnson, Piggott, Haroutunian, Buxbaum, Nãsland, Davis, Gotti, Clementi, Tzartos, Cohen, Soreq, Jaros, Perry, Ballard, McKeith, Court,

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 alpha4 (but not alpha3 or 7) subunit immunoreactivity and of nicotine or epibatidine binding but not alpha-bungarotoxin binding. Epibatidine binding is inversely correlated with clinical dementia ratings and with the level of Abeta1-42, 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 alpha4 subunit immunoreactivity. Tobacco use in normal elderly individuals is associated with increased alpha4 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 alpha4 subunit in beta-amyloidosis but not in nigro-striatal dopaminergic degeneration.[1]

References

Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy body diseases. Perry, E., Martin-Ruiz, C., Lee, M., Griffiths, M., Johnson, M., Piggott, M., Haroutunian, V., Buxbaum, J.D., Nãsland, J., Davis, K., Gotti, C., Clementi, F., Tzartos, S., Cohen, O., Soreq, H., Jaros, E., Perry, R., Ballard, C., McKeith, I., Court, J. Eur. J. Pharmacol. (2000) [Pubmed]

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