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. 2009 Dec;73(6):917-20.
doi: 10.1016/j.mehy.2009.06.046. Epub 2009 Jul 31.

The X-chromosome instability phenotype in Alzheimer's disease: a clinical sign of accelerating aging?

Vladan P Bajić  1 , Biljana Spremo-Potparević, Lada Zivković, David J Bonda, Sandra L Siedlak, Gemma Casadesus, Hyoung-Gon Lee, Mark A Smith
Affiliations

The X-chromosome instability phenotype in Alzheimer's disease: a clinical sign of accelerating aging?

Vladan P Bajić et al. Med Hypotheses. 2009 Dec.

Abstract

Premature centromere division, or premature centromere separation (PCS), occurs when chromatid separation is dysfunctional, occurring earlier than usual during the interphase stage of mitosis. This phenomenon, seen in Robert's syndrome and various cancers, has also been documented in peripheral as well as neuronal cells of Alzheimer's disease (AD). In the latter instances, fluorescent in situ hybridization (FISH), applied to the centromere region of the X-chromosome in interphase nuclei of lymphocytes from peripheral blood in AD patients, demonstrated premature chromosomal separation before mitotic metaphase directly after completion of DNA replication in G(2) phase of the cell cycle. Furthermore, and perhaps unexpectedly given the presumptive post-mitotic status of terminally differentiated neurons, neurons in AD patients also showed significantly increased levels of PCS of the X-chromosome. Taken together with other phenomena such as cell cycle re-activation and ectopic re-expression of cyclins and cyclin dependent proteins, we propose that AD is an oncogenic phenotype leading to accelerated aging of the affected brain.

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Conflict of interest statement

Conflicts of Interest/Role of the Funding Source: None of the authors have a financial or personal relationship with other people or organizations that could inappropriately influence this work.

The sources of funding have no role in the collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication.

Figures

Figure 1
Figure 1
Premature centromere separation (PCS) demonstrates genomic instability in AD patients. Arrowhead indicates prematurely separated chromosome with two centromeres, one for each sister chromatid. Surrounding chromosomes are depicted in their normal, undivided states, each with one centromere.
Figure 2
Figure 2
Fluorescent signals for the centromeric region of chromosome X on interphase nuclei in AD patients and control group. a) interphase nuclei in AD female contains two bipartite signals (PCD+ on both X chromosome);b) interphase nuclei in AD female with a nuclei and one dot like signal (PCD-), and one bipartite signal (PCD+);c) interphase nuclei of a female from the control group with two separated dot like signals (PCD-);d) interphase nuclei of a AD male with one bi-partite signal (PCD+); e) interphase nuclei of a male from the control group with one dot like signal (PCD-).
See this image and copyright information in PMC

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