. A novel nicotinic acetylcholine receptor subtype in basal forebrain cholinergic neurons with high sensitivity to amyloid peptides. J Neurosci. 2009 Jan 28;29(4):918-29. PubMed.

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  1. In this study, Liu et al. demonstrate the co-assembly of α7 nicotinic receptors and β2 subunits. The increasing knowledge of the functional role of α7 nicotinic receptors in brain is fascinating. It appears more relevant that the α7 nicotinic receptors also may colocalize with β2 subunits, similar to the other forms of nicotinic subunits expressed in brain, rather than solely existing in monomeric forms.

    Interestingly enough, Liu et al. observed that it was the oligomeric form of Aβ, in such low concentrations as 1 nM, that inhibited the α7β2 nicotinic receptors in rodent brain. An important question is how relevant these observations are for the Alzheimer brain. Earlier studies have demonstrated a decrease in α7 nicotinic receptors in the neurons but an increase in α7 nicotinic receptors in the astrocytes (Teaktong et al., 2003; Yu et al., 2005). The increase of α7 nicotinic receptors was especially high in Alzheimer patients with APPswe mutations compared to patients with sporadic Alzheimer’s disease (Yu et al., 2005). Do the heteromeric forms of α7 receptors exist in Alzheimer brains?

    Is there a different distribution of monomeric and heteromeric α7 nicotinic receptors in neurons versus astrocytes? The α7 nicotinic receptors have also been suggested to be required for Aβ-promoted NMDA endocytosis (Snyder et al., 2005). Thus, several independent studies support an important link between α7 nicotinic receptors and Aβ, both regarding toxicity as well as neuroprotective mechanisms. The search for selective α7 nicotinic receptor as new drug targets in Alzheimer disease might be very rewarding.

    References:

    . Alzheimer's disease is associated with a selective increase in alpha7 nicotinic acetylcholine receptor immunoreactivity in astrocytes. Glia. 2003 Jan 15;41(2):207-11. PubMed.

    . High selective expression of alpha7 nicotinic receptors on astrocytes in the brains of patients with sporadic Alzheimer's disease and patients carrying Swedish APP 670/671 mutation: a possible association with neuritic plaques. Exp Neurol. 2005 Mar;192(1):215-25. PubMed.

    . Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci. 2005 Aug;8(8):1051-8. PubMed.