Differential physiologic responses of α7 nicotinic acetylcholine receptors to β‐amyloid1–40 and β‐amyloid1–42

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Abstract
The β‐amyloid peptides (Aβ), Aβ1–40 and Aβ1–42, have been implicated in Alzheimer's disease (AD) pathology. Although Aβ1–42 is generally considered to be the pathological peptide in AD, both Aβ1–40 and Aβ1–42 have been used in a variety of experimental models without discrimination. Here we show that monomeric or oligomeric forms of the two Aβ peptides, when interact with the neuronal cation channel, α7 nicotinic acetylcholine receptors (α7nAChR), would result in distinct physiologic responses as measured by acetylcholine release and calcium influx experiments. While Aβ1–42 effectively attenuated these α7nAChR‐dependent physiology to an extent that was apparently irreversible, Aβ1–40 showed a lower inhibitory activity that could be restored upon washings with physiologic buffers or treatment with α7nAChR antagonists. Our data suggest a clear pharmacological distinction between Aβ1–40 and Aβ1–42. © 2003 Wiley Periodicals, Inc. J Neurobiol 55: 25–30, 2003