X chromosome aneuploidy in the Alzheimer’s disease brain

Molecular Cytogenetics

Ivan Y Iourov¹  Alexei D Kolotii⁴  Thomas Liehr²  Svetlana G Vorsanova³  Yuri B Yurov³ 

[1] Department of Medical Genetics, Russian Medical Academy of Postgraduate Education, 123995 Moscow, Russia;Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Kollegiengasse 10, D-07743 Jena, Germany;Moscow City University of Psychology and Education, 127051 Moscow, Russia;Institute of Pediatrics and Children Surgery, Ministry of Health of the Russian Federation, 125412 Moscow, Russia

关键词: Aging;    Molecular cytogenetics;    Chromosome X;    Chromosome instability;    Brain;    Aneuploidy;    Alzheimer’s disease;   

Others  :  1150236
DOI  :  10.1186/1755-8166-7-20

 received in 2013-12-30, accepted in 2014-02-11,  发布年份 2014

【 摘 要 】

Background

Although the link between brain aging and Alzheimer’s disease (AD) is a matter of debate, processes hallmarking cellular and tissue senescence have been repeatedly associated with its pathogenesis. Here, we have studied X chromosome aneuploidy (a recognized feature of aged cell populations) in the AD brain.

Results

Extended molecular neurocytogenetic analyses of X chromosome aneuploidy in 10 female AD as well as 10 age and sex matched female control postmortem brain samples was performed by multiprobe/quantitative FISH. Additionally, aneuploidy rate in the brain samples of 5 AD and as 5 age and sex matched control subjects were analyzed by interphase chromosome-specific multicolor banding (ICS-MCB). Totally, 182,500 cells in the AD brain and 182,500 cells in the unaffected brain were analyzed. The mean rate of X chromosome aneuploidy in AD samples was approximately two times higher than in control (control: mean - 1.32%, 95% CI 0.92- 1.71%; AD: mean - 2.79%, 95% CI 1.88-3.69; P = 0.013). One AD sample demonstrated mosaic aneuploidy of chromosome X confined to the hippocampus affecting about 10% of cells. ICS-MCB confirmed the presence of X chromosome aneuploidy in the hippocampal tissues of AD brain (control: mean - 1.74%, 95% CI 1.38- 2.10%; AD: mean - 4.92%, 95% CI 1.14-8.71; P < 0.001).

Conclusions

Addressing X chromosome number variation in the brain, we observed that somatically acquired (post-zygotic) aneuploidy causes large-scale genomic alterations in neural cells of AD patients and, therefore, can be involved in pathogenesis of this common neurodegenerative disorder. In the context of debates about possible interplay between brain aging and AD neurodegeneration, our findings suggest that X chromosome aneuploidy can contribute to both processes. To this end we conclude that mosaic aneuploidy in the brain is a new non-heritable genetic factor predisposing to AD.

【 授权许可】

   
2014 Yurov et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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