I think the findings of this study are quite promising. The study demonstrates that human amyloid-β peptides can disrupt olfactory neuronal pathways in mice, even without forming the plaques that characterize Alzheimer's disease. Furthermore, these disruptions led to a measurable decline in the animals' ability to smell.

Hopefully, the authors of the study will be taking the next step in determining whether similar changes in olfactory neurons and a resultant decline in smell are also seen in people expressing amyloid-β peptides, but not necessarily the plaques.

I also hope that this discovery will generate additional interest in identifying ways to detect and treat Alzheimer's disease in its early stages, even before the accumulation of amyloid plaques begins.

View all comments by Gordon H. Sun

The authors demonstrate convincingly an Aβ-induced alteration of the olfactory sensory system. Among the various transgenic animal models presented, CORMAP mice might represent a valuable model for screening of potential drugs to restore the network function/connectivity.

It would be interesting to see, in future studies, whether the observed phenotype is reversible in a tau-null background, i.e., whether tau is an important mediator of Aβ-induced changes in connectivity (1,2). Also, it might be interesting to evaluate the influence of different, potentially more amyloidogenic forms of Aβ (3,4) applying the AAV injection technique.

References:
1. Vossel KA, Zhang K, Brodbeck J, Daub AC, Sharma P, Finkbeiner S, Cui B, Mucke L. Tau reduction prevents Abeta-induced defects in axonal transport. Science. 2010 Oct 8;330(6001):198. Abstract

2. Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, Gerstein H, Yu GQ, Mucke L. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science. 2007 May 4;316(5825):750-4. Abstract

3. Alexandru A, Jagla W, Graubner S, Becker A, Bäuscher C, Kohlmann S, Sedlmeier R, Raber KA, Cynis H, Rönicke R, Reymann KG, Petrasch-Parwez E, Hartlage-Rübsamen M, Waniek A, Rossner S, Schilling S, Osmand AP, Demuth HU, von Hörsten S. Selective hippocampal neurodegeneration in transgenic mice expressing small amounts of truncated Aβ is induced by pyroglutamate-Aβ formation. J Neurosci. 2011 Sep 7;31(36):12790-801. Abstract

4. Nussbaum JM, Schilling S, Cynis H, Silva A, Swanson E, Wangsanut T, Tayler K, Wiltgen B, Hatami A, Rönicke R, Reymann K, Hutter-Paier B, Alexandru A, Jagla W, Graubner S, Glabe CG, Demuth HU, Bloom GS. Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β. Nature. 2012 May 31;485(7400):651-5. Abstract

View all comments by Stephan Schilling