title: Single-cell whole genome sequencing reveals no evidence for common aneuploidy in normal and Alzheimer's disease neurons.
abstract: Alzheimer's disease (AD) is a neurodegenerative disease of the brain and the most common form of dementia in the elderly. Aneuploidy, a state in which cells have an abnormal number of chromosomes, has been proposed to play a role in neurodegeneration in AD patients. Several studies using fluorescence in situ hybridization have shown that the brains of AD patients contain an increased number of aneuploid cells. However, because the reported rate of aneuploidy in neurons ranges widely, a more sensitive method is needed to establish a possible role of aneuploidy in AD pathology.
  
  
  
  In the current study, we used a novel single-cell whole genome sequencing (scWGS) approach to assess aneuploidy in isolated neurons from the frontal cortex of normal control individuals (n = 6) and patients with AD (n = 10). The sensitivity and specificity of our method was shown by the presence of three copies of chromosome 21 in all analyzed neuronal nuclei of a Down's syndrome sample (n = 36). Very low levels of aneuploidy were found in the brains from control individuals (n = 589) and AD patients (n = 893). In contrast to other studies, we observe no selective gain of chromosomes 17 or 21 in neurons of AD patients.
  
  
  
  scWGS showed no evidence for common aneuploidy in normal and AD neurons. Therefore, our results do not support an important role for aneuploidy in neuronal cells in the pathogenesis of AD. This will need to be confirmed by future studies in larger cohorts.
authors.affiliation: European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands.
authors.forename: Hilda
authors.initials: H
authors.lastname: van den Bos
authors.affiliation: European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands.
authors.forename: Diana C J
authors.initials: DC
authors.lastname: Spierings
authors.affiliation: European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands.|Institute for Computational Biology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Taudt
authors.affiliation: European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Bakker
authors.affiliation: European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands.
authors.forename: David
authors.initials: D
authors.lastname: Porubský
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, V5Z 1 L3, Canada.
authors.forename: Ester
authors.initials: E
authors.lastname: Falconer
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, V5Z 1 L3, Canada.
authors.forename: Carolina
authors.initials: C
authors.lastname: Novoa
authors.affiliation: European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands.
authors.forename: Nancy
authors.initials: N
authors.lastname: Halsema
authors.affiliation: European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands.
authors.forename: Hinke G
authors.initials: HG
authors.lastname: Kazemier
authors.affiliation: European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands.
authors.forename: Karina
authors.initials: K
authors.lastname: Hoekstra-Wakker
authors.affiliation: European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands.
authors.forename: Victor
authors.initials: V
authors.lastname: Guryev
authors.affiliation: Section of Pathology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands.
authors.forename: Wilfred F A
authors.initials: WF
authors.lastname: den Dunnen
authors.affiliation: European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands.
authors.forename: Floris
authors.initials: F
authors.lastname: Foijer
authors.affiliation: European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands.|Institute for Computational Biology, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: Maria Colomé
authors.initials: MC
authors.lastname: Tatché
authors.affiliation: Section Medical Physiology, Department of Neuroscience, University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands.
authors.forename: Hendrikus W G M
authors.initials: HW
authors.lastname: Boddeke
authors.affiliation: European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands. p.m.lansdorp@umcg.nl.|Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, V5Z 1 L3, Canada. p.m.lansdorp@umcg.nl.|Division of Hematology, Department of Medicine, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada. p.m.lansdorp@umcg.nl.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Lansdorp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000782:Aneuploidy; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D017422:Sequence Analysis, DNA / Q000379:methods*; D059010:Single-Cell Analysis / Q000379:methods*
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer’s disease; Aneuploidy; Brain; Neurons; Single-cell sequencing