title: Super-resolution structure of DNA significantly differs in buccal cells of controls and Alzheimer's patients.
abstract: The advent of super-resolution microscopy allowed for new insights into cellular and physiological processes of normal and diseased cells. In this study, we report for the first time on the super-resolved DNA structure of buccal cells from patients with Alzheimer's disease (AD) versus age- and gender-matched healthy, non-caregiver controls. In this super-resolution study cohort of 74 participants, buccal cells were collected and their spatial DNA organization in the nucleus examined by 3D Structured Illumination Microscopy (3D-SIM). Quantitation of the super-resolution DNA structure revealed that the nuclear super-resolution DNA structure of individuals with AD significantly differs from that of their controls (p < 0.05) with an overall increase in the measured DNA-free/poor spaces. This represents a significant increase in the interchromatin compartment. We also find that the DNA structure of AD significantly differs in mild, moderate, and severe disease with respect to the DNA-containing and DNA-free/poor spaces. We conclude that whole genome remodeling is a feature of buccal cells in AD.
authors.affiliation: Department of Medicine (Geriatrics) and Neuroscience Center, Queen's University, SMOL, Kingston, Ontario, Canada.
authors.forename: Angeles
authors.initials: A
authors.lastname: Garcia
authors.affiliation: Department of Physiology and Pathophysiology, Manitoba Institute of Cell Biology, University of Manitoba, CancerCare Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Physiology and Pathophysiology, Manitoba Institute of Cell Biology, University of Manitoba, CancerCare Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Amanda
authors.initials: A
authors.lastname: Righolt
authors.affiliation: Department of Physiology and Pathophysiology, Manitoba Institute of Cell Biology, University of Manitoba, CancerCare Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Christiaan
authors.initials: C
authors.lastname: Righolt
authors.affiliation: Department of Physiology and Pathophysiology, Manitoba Institute of Cell Biology, University of Manitoba, CancerCare Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Kalaw
authors.affiliation: Department of Physiology and Pathophysiology, Manitoba Institute of Cell Biology, University of Manitoba, CancerCare Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Shubha
authors.initials: S
authors.lastname: Mathur
authors.affiliation: Department of Medicine (Geriatrics) and Neuroscience Center, Queen's University, SMOL, Kingston, Ontario, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McAvoy
authors.affiliation: Department of Medicine (Geriatrics) and Neuroscience Center, Queen's University, SMOL, Kingston, Ontario, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Anderson
authors.affiliation: Department of Medicine (Geriatrics) and Neuroscience Center, Queen's University, SMOL, Kingston, Ontario, Canada.
authors.forename: Angela
authors.initials: A
authors.lastname: Luedke
authors.affiliation: Department of Medicine (Geriatrics) and Neuroscience Center, Queen's University, SMOL, Kingston, Ontario, Canada.
authors.forename: Justine
authors.initials: J
authors.lastname: Itorralba
authors.affiliation: Department of Physiology and Pathophysiology, Manitoba Institute of Cell Biology, University of Manitoba, CancerCare Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Sabine
authors.identifier: http://orcid.org/0000-0002-5797-2201
authors.initials: S
authors.lastname: Mai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000737:chemistry / Q000648:ultrastructure*; D002843:Chromatin / Q000235:genetics* / Q000302:isolation & purification / Q000648:ultrastructure*; D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification / Q000648:ultrastructure*; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008853:Microscopy / Q000379:methods; D008875:Middle Aged; D009061:Mouth Mucosa / Q000737:chemistry / Q000648:ultrastructure*; D009690:Nucleic Acid Conformation; D012720:Severity of Illness Index
chemical_list: D002843:Chromatin; D004247:DNA
keywords: Alzheimer's disease; buccal cells; super-resolution microscopy