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Cited by 93Alzheimer's disease research and treatmentsOlfactory and Sensory Function StudiesNeuroscience and Neuropharmacology Research

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

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Cao, Luxiang, Schrank, Benjamin R., Rodriguez, Steve, Benz, Eric G., Moulia, Thomas W., Rickenbacher, Gregory T., Gomez, Alexis C., Levites, Yona +5 more·2012·Nature Communications
DOI 10.1038/ncomms2013PMC PMC3529477
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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.

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  • Aβ peptides in various forms have been linked to alterations in cerebral calcium homeostasis, axonal guidance, axonal transport, and/or synaptic signaling.

    “A␤ peptides in various forms have been linked to alterations in cerebral calcium homeostasis (Kuchibhotla et al., 2008), axonal guidance (Cao et al., 2012), axonal transport, and/or synaptic signaling (Knobloch et al., 2007a), processes that ultimately might translate into impaired neural function.”

    From Early Alterations in Functional Connectivity and White Matter Structure in a Transgenic Mouse Model of Cerebral Amyloidosis (2014) · cites this paper as Cao et al., 2012

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Authors
Cao, L., Schrank, B. R., Rodriguez, S., Benz, E. G., Moulia, T. W., Rickenbacher, G. T., Gomez, A. C., Levites, Y., Edwards, S. R., Golde, T. E., Hyman, B. T., Barnea, G., & Albers, M. W.
Affiliations
  • Harvard University (US)
  • University of Florida (US)
  • Brown University (US)
Corresponding author
Albers, Mark W.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2012-08-21
Volume
3
Issue
1
Pages
1009-1009
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms2013
PMC
PMC3529477
OpenAlex
W2102053742
Cited by
93
References
3
Citations by year
2026: 6 · 2025: 5 · 2024: 7 · 2023: 3 · 2022: 6 · 2021: 18 · 2020: 4 · 2019: 8 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 15 · 2013: 4 · 2012: 1
FWCI
5.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Rappaport Foundation
  • National Institutes of Health (1dp2od006662-01)
  • National Institute on Aging (P30AG036449, P50AG005134, P30AG062421)
  • National Institute on Deafness and Other Communication Disorders (K08 DC04807, K08DC004807)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
amyloid-beta, olfactory sensory neurons, olfactory epithelium, neuronal connectivity, amyloid plaques, Alzheimer's disease, axon targeting, olfactory sensitivity, soluble amyloid-beta, preclinical Alzheimer's disease
MeSH terms
Alzheimer Disease, Animals, Axons, Disease Models, Animal, Female, Humans, Male, Mice, Transgenic, Neural Conduction, Sensory Receptor Cells, Amyloid beta-Peptides, Mice, Olfactory Perception, Plaque, Amyloid

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