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

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Aging Clinical and Experimental Research Aims and scope Submit manuscript

Abstract

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.

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Acknowledgments

We are grateful to thank Mr. Brian Quinn for his linguistic advice. This work was supported by grants from the Ministry of Education, Science, and Culture of Japan (#23590885) and the National Natural Science Fund (NSFC) (81170329/H2501).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. 309th Hospital of Chinese People’s Liberation Army, Beijing, 100091, China

    Jing-Zhi Guan

  2. Nanlou Neurology Department, Chinese PLA General Hospital, Beijing, China

    Wei Ping Guan

  3. Division of Cardiovascular, Respiratory and Geriatric Medicine, Kyushu University Beppu Hospital, Beppu, Oita, 874-0838, Japan

    Toyoki Maeda & Naoki Makino

Authors
  1. Jing-Zhi Guan
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  2. Wei Ping Guan
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  3. Toyoki Maeda
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  4. Naoki Makino
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Corresponding author

Correspondence to Toyoki Maeda.

Additional information

J.-Z. Guan, W. P. Guan and T. Maeda contributed equally to this article.

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Guan, JZ., Guan, W.P., Maeda, T. et al. Analysis of telomere length and subtelomeric methylation of circulating leukocytes in women with Alzheimer’s disease. Aging Clin Exp Res 25, 17–23 (2013). https://doi.org/10.1007/s40520-013-0006-0

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  • DOI: https://doi.org/10.1007/s40520-013-0006-0

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