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Hypothesis and Theory ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.01092

Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative and Neurodevelopmental Disorders

 Huntington Potter1, 2, 3*, Heidi J. Chial1, 3,  Julbert Caneus4, Mihret Elos1, 3,  Nina Elder1, 3, Sergiy Borysov5 and  Antoneta Granic6, 7, 8
  • 1Rocky Mountain Alzheimer’s Disease Center, School of Medicine, University of Colorado, United States
  • 2Linda Crnic Institute for Down Syndrome​​, School of Medicine, University of Colorado, United States
  • 3Department of Neurology, School of Medicine, University of Colorado, United States
  • 4NanoScience Technology Center, University of Central Florida, United States
  • 5Saint Leo University, United States
  • 6NIHR Newcastle Biomedical Research Centre, United Kingdom
  • 7Institute for Ageing, Newcastle University, United Kingdom
  • 8Newcastle upon Tyne Hospitals NHS Foundation Trust, United Kingdom

Evidence from multiple laboratories has accumulated to show that mosaic neuronal aneuploidy and consequent apoptosis characterizes and may underlie neuronal loss in many neurodegenerative diseases, particularly Alzheimer’s disease and frontotemporal dementia. Furthermore, several neurodevelopmental disorders, including Seckel syndrome, ataxia telangiectasia, Nijmegen breakage syndrome, Niemann-Pick type C, and Down syndrome, have been shown to also exhibit mosaic aneuploidy in neurons in the brain and in other cells throughout the body. Together, these results indicate that both neurodegenerative and neurodevelopmental disorders with apparently different pathogenic causes share a cell cycle defect that leads to mosaic aneuploidy in many cell types. When such mosaic aneuploidy arises in neurons in the brain, it promotes apoptosis and may at least partly underlie the cognitive deficits that characterize the neurological symptoms of these disorders. These findings have implications for both diagnosis and treatment/prevention.

Keywords: Alzheimer ' s disease, Mosaic aneuploidy, Frontal temporal lobar degeneration, Neuronal apoptosis, Huntington's disease (HD)

Received: 12 Sep 2019; Accepted: 09 Oct 2019.

Copyright: © 2019 Potter, Chial, Caneus, Elos, Elder, Borysov and Granic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Huntington Potter, Rocky Mountain Alzheimer’s Disease Center, School of Medicine, University of Colorado, Aurora, 80045, Colorado, United States,