Analysis of telomere length and subtelomeric methylation of circulating leukocytes in women with Alzheimer’s disease

• Published in: Aging clinical and experimental research Vol. 25; no. 1; pp. 17 - 23
• Main Authors: Guan, Jing-Zhi, Guan, Wei Ping, Maeda, Toyoki, Makino, Naoki
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing AG 01.04.2013; Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Aging; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Case-Control Studies; DNA Methylation; Female; Geriatrics/Gerontology; Humans; Leukocytes - metabolism; Leukocytes - pathology; Medicine; Medicine & Public Health; Original Article; Telomerase; Telomere Homeostasis; Yeast; DNA methylation; Alzheimer’s disease; Female gender; Telomere; Subtelomere
• ISSN: 1720-8319; 1594-0667; 1720-8319
• DOI: 10.1007/s40520-013-0006-0

Backgrounds and aims Telomere attrition proceeds with the aging process, and is also associated with aging disease conditions, such as Alzheimer’s disease (AD). The aging process also affects subtelomeric methylation status. In the present study, the telomere length and the subtelomeric methylation status in female AD patients were analyzed to see how AD affects telomere structure. Methods Terminal restriction fragment length of 23 AD patients’ peripheral leukocytes was analyzed with methylation sensitive- and insensitive-isoschizomer by Southern blot. Results AD patients were found to have normal mean telomere lengths (controls; 6.4 ± 0.9 kb, AD; 6.1 ± 0.8 kb, p  = 0.131), a proportionally decreased number of the longest telomeres (>9.4 kb) (controls; 30.3 ± 7.9 %, AD; 24.4 ± 8.3 %, p  = 0.013), increased medium-sized telomeres (controls; 51.7 ± 3.3 %, AD 55.5 ± 6.4 %, p  = 0.015) and unchanged numbers of the shortest telomeres (<4.4 kb) (controls; 18.0 ± 7.8, AD; 20.2 ± 8.9 %, p  = 0.371) in their peripheral leukocytes. The subtelomeres of telomeres in the shortest range (<4.4 kb) were more methylated in AD subjects than in controls (controls; 0.21 ± 0.23, AD; 0.41 ± 0.26, p  = 0.016). Conclusions These results may indicate that AD contributes to the loss of cells bearing the shortest telomeres, with hypomethylation of subtelomeres occurring in addition to telomere attrition, resulting in an apparent normal mean telomere length in AD patients. The relatively high subtelomeric methylation status of the shortest telomeres in peripheral blood leukocytes may be a characteristic of AD. This report demonstrates that the epigenetic status of the telomeric region is affected by disease conditions.