Cao L, Schrank BR, Rodriguez S, Benz EG, Moulia TW, Rickenbacher GT, Gomez AC, Levites Y, Edwards SR, Golde TE, Hyman BT, Barnea G, Albers MW. Aβ alters the connectivity of olfactory neurons in the absence of amyloid plaques in vivo. Nat Commun. 2012;3:1009. PubMed.
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Robert Wood Johnson Foundation-U.S. Department of Veterans Affairs
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.
Fraunhofer Institute for Cell Therapy and Immunology
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.
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