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Skewed X-Chromosome Inactivation in Women Affected by Alzheimers Disease

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Authors
Bajić, Vladan P.
Mandušić, Vesna
Stefanova, Elka
Božović, Ana M.
Davidović, Radoslav S.
Živković, Lada
Cabarkapa, Andrea
Spremo-Potparević, Biljana
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Abstract
X-chromosome instability has been a long established feature in Alzheimers disease ( AD). Premature centromere division and aneuploidy of the X-chromosome has been found in peripheral blood lymphocytes and neuronal tissue in female AD patients. Interestingly, only one chromosome of the X pair has been affected. These results raised a question, Is the X-chromosome inactivation pattern altered in peripheral blood lymphocytes ofwomen affected by AD? To address this question, we analyzed the methylation status of androgen receptor promoter which may show us any deviation from the 50 : 50% X inactivation status in peripheral blood lymphocytes ofwomen with AD. Our results showed skewed inactivation patterns ( GT 90%). These findings suggest that an epigenetic alteration on the inactivation centers of the X-chromosome (or skewing) relates not only to aging, by might be a novel property that could account for the higher incidence of AD in women.
Keywords:
Alzheimers disease / aneuploidy / methylation specific qPCR / X-chromosome / X-chromosome skewing
Source:
Journal of Alzheimers Disease, 2015, 43, 4, 1251-1259
Projects:
  • Cell Cycle Aberrations and the Impact of Oxidative Stress in Neurodegenerative Processes and Malignant Transformation of the Cell (RS-173034)
  • Molecular determinants for tumor marker design (RS-173049)

DOI: 10.3233/JAD-141674

ISSN: 1387-2877 (print); 1875-8908 (electronic)

PubMed: 25159673

WoS: 000346857400014

Scopus: 2-s2.0-84919880287
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http://vinar.vin.bg.ac.rs/handle/123456789/314
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