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Progressive signaling changes in the olfactory nerve of patients with Alzheimer’s disease

  • Bathini, Praveen Department of Medicine, University of Fribourg, Switzerland
  • Mottas, Antoine Department of Medicine, University of Fribourg, Switzerland
  • Jaquet, Muriel Department of Neurology Research, Swiss Integrative Center for Human Health, Fribourg, Switzerland
  • Brai, Emanuele Neuro-Bio Ltd, Oxford, UK
  • Alberi, Lavinia Department of Medicine, University of Fribourg, Switzerland - Department of Neurology Research, Swiss Integrative Center for Human Health, Fribourg, Switzerland
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    01.04.2019
Published in:
  • Neurobiology of Aging. - 2019, vol. 76, p. 80–95
English Olfaction declines with aging and appears to be a prodromal sign of cognitive decline in progressive neurodegenerative diseases. Nevertheless, very little is known about the pathophysiological changes underlying smell loss that may reflect early network dysfunction. A cross-sectional histoanatomical study was conducted on postmortem olfactory nerves of patients with increasing severity of dementia from mild cognitive impairment (MCI) to moderate and severe Alzheimer's disease. The olfactory bulbs and tracts show a prominent and progressive tauopathy in contrast to a weaker amyloid pathology localized to the glomerular region. Topological analysis of Notch signaling components reveals a transient increase in Jagged1 expression in mitral cells of the olfactory bulb of patients with MCI and a gradual decline onwards. Analysis of the olfactory tract reveals an abundance of corpora amylacea, which declines starting from the MCI stage. With the increasing severity of dementia, corpora amylacea are characterized by a gradual shift in cytoskeletal proteins, tau, MAP2 and glial fibrillary acid protein, as well as by a decrease in their Reelin and Jagged1 content. Our research indicates that the olfactory nerve undergoes early and sequential morphological and signaling alterations that correlate with the development of dementia suggesting that this structure may capture and propagate neuronal network imbalances to connected higher brain centers of the entorhinal cortex and hippocampus.
Faculty
Faculté des sciences et de médecine
Department
Médecine 3ème année
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/307724
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