Skewed X-Chromosome Inactivation in Women Affected by Alzheimer's Disease

Abstract

X-chromosome instability has been a long established feature in Alzheimer's 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 (>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.