The study by Pigino et al. study elegantly highlights a possible mechanism by which Aβ oligomers can influence axonal transport. Though the validity of intracellular Aβ is debatable in the context of human AD pathology, Pigino et al. convincingly show that in a simple model-system of axonal transport, nanomolar levels of Aβ can influence transport; they also provide convincing evidence for the involvement of a specific signaling cascade in this process. The paper is a must-read!

View all comments by Subhojit Roy

We have recently observed that the membrane surfaces of neurons (mainly pyramidal cells) in contact with plaques lack GABAergic perisomatic synapses (Garcia-Marin et al., 2009). Indeed, a large proportion of plaques are in contact with neurons, and of the several hundred neurons that we found to come into contact with plaques, in no cases were perisomatic terminals found at the surface of the neuron that was directly touching the plaque. Since these perisomatic synapses are thought to exert a strong influence on the output of pyramidal cells, their loss may lead to the hyperactivity of the neurons in contact with plaques. These findings are consistent with the in-vivo calcium-imaging experiments of Busche et al. (2008).

References:
Busche, M.A., Eichhoff, G., Adelsberger, H., Abramowski, D., Wiederhold, K.H., Haass, C., Staufenbiel, M., Konnerth, A., and Garaschuk, O. (2008). Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease. Science 321, 1686-1689. Abstract

Garcia-Marin V, Blazquez-Llorca L, Rodriguez J, Boluda S, Muntane G, Ferrer I and DeFelipe J (2009) Diminished perisomatic GABAergic terminals on cortical neurons adjacent to amyloid plaques. Front. Neuroanat. 3:28. Abstract

View all comments by Javier DeFelipe