Aβ alters the connectivity of olfactory neurons in the absence of amyloid plaques in vivo

Luxiang Cao, Benjamin R. Schrank, Steve Rodriguez, Eric G. Benz, Thomas W. Moulia, Gregory T. Rickenbacher, Alexis C. Gomez, Yona Levites, Sarah R. Edwards, Todd E. Golde, Bradley T. Hyman, Gilad Barnea and Mark W. Albers ()
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Luxiang Cao: MassGeneral Institute of Neurodegenerative Disease, Harvard Medical School
Benjamin R. Schrank: MassGeneral Institute of Neurodegenerative Disease, Harvard Medical School
Steve Rodriguez: MassGeneral Institute of Neurodegenerative Disease, Harvard Medical School
Eric G. Benz: MassGeneral Institute of Neurodegenerative Disease, Harvard Medical School
Thomas W. Moulia: MassGeneral Institute of Neurodegenerative Disease, Harvard Medical School
Gregory T. Rickenbacher: MassGeneral Institute of Neurodegenerative Disease, Harvard Medical School
Alexis C. Gomez: MassGeneral Institute of Neurodegenerative Disease, Harvard Medical School
Yona Levites: University of Florida
Sarah R. Edwards: MassGeneral Institute of Neurodegenerative Disease, Harvard Medical School
Todd E. Golde: University of Florida
Bradley T. Hyman: MassGeneral Institute of Neurodegenerative Disease, Harvard Medical School
Gilad Barnea: Brown University
Mark W. Albers: MassGeneral Institute of Neurodegenerative Disease, Harvard Medical School

Nature Communications, 2012, vol. 3, issue 1, 1-10

Abstract: Abstract The amyloid beta peptide aggregates into amyloid plaques at presymptomatic stages of Alzheimer's disease, but the temporal relationship between plaque formation and neuronal dysfunction is poorly understood. Here we demonstrate that the connectivity of the peripheral olfactory neural circuit is perturbed in mice overexpressing human APPsw (Swedish mutation) before the onset of plaques. Expression of human APPsw exclusively in olfactory sensory neurons also perturbs connectivity with associated reductions in odour-evoked gene expression and olfactory acuity. By contrast, olfactory sensory neuron axons project correctly in mice overexpressing wild-type human amyloid precursor protein throughout the brain and in mice overexpressing M671V human APP, a missense mutation that reduces amyloid beta production, exclusively in olfactory sensory neurons. Furthermore, expression of Aβ40 or Aβ42 solely in the olfactory epithelium disrupts the olfactory sensory neuron axon targeting. Our data indicate that altering the structural connectivity and function of highly plastic neural circuits is one of the pleiotropic actions of soluble human amyloid beta.

Date: 2012
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DOI: 10.1038/ncomms2013

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