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Article type: Research Article
Authors: Mathur, Shubhaa | Glogowska, Aleksandraa | McAvoy, Elizabethb | Righolt, Christiaana; c | Rutherford, Jaclyna | Willing, Corneliaa | Banik, Upamaa | Ruthirakuhan, Myurib | Mai, Sabinea; * | Garcia, Angelesb; *
Affiliations: [a] Manitoba Institute of Cell Biology, The University of Manitoba, CancerCare Manitoba, Winnipeg, MB, Canada | [b] Department of Medicine (Geriatrics) and Neuroscience Centre, Queen's University, SMOL, Kingston, ON, Canada | [c] Department of Imaging Science & Technology, Delft University of Technology, CJ Delft, The Netherlands
Correspondence: [*] Correspondence to: Dr. Sabine Mai, 675 McDermot Ave, Winnipeg, Manitoba R3E 0V9, Canada. Tel.: +1 204 787 2135; Fax: +1 204 787 2190; E-mail: [email protected]; Dr. Angeles Garcia, 340 Union St, Kingston, Ontario K7L 3A5, Canada. Tel.: +1 613 544 5220; Fax: +1 613 544 4017; E-mail: [email protected].
Abstract: Using three-dimensional (3D) telomeric analysis of buccal cells of 82 Alzheimer's disease (AD) patients and cognitively normal age and gender-matched controls, we have for the first time examined changes in the 3D nuclear telomeric architecture of buccal cells among levels of AD severity based on five 3D parameters: i) telomere length, ii) telomere number, iii) telomere aggregation, iv) nuclear volume, and v) a/c ratio, a measure of spatial telomere distribution. Our data indicate that matched controls have significantly different 3D telomere profiles compared to mild, moderate, and severe AD patients (p < 0.0001). Distinct profiles were also evident for each AD severity group. An increase in telomere number and aggregation concomitant with a decrease in telomere length from normal to severe AD defines the individual stages of the disease (p < 0.0001).
Keywords: Alzheimer's disease, buccal mucosa, fluorescent in situ hybridization, genomic instability, three-dimensional image, telomeres
DOI: 10.3233/JAD-130866
Journal: Journal of Alzheimer's Disease, vol. 39, no. 1, pp. 35-48, 2014
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