Premature centromere division of the X chromosome in neurons in Alzheimer’s disease

Spremo-Potparević, Bilijana; Živković, Lada; Djelić, Ninoslav; Plećaš-Solarović, Bosiljka; Smith, Mark A.; Bajić, Vladan

doi:10.1111/j.1471-4159.2008.05555.x

Cited by 39 publications

(39 citation statements)

References 59 publications

(103 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CIN occurs when processes that maintain chromosome integrity and regulate chromosome segregation are disrupted [1]. In Alzheimer's disease, some features of chromosome instability have been shown in the cells of the nervous system [2,3,4,5], but also in cells of peripheral tissues [6,7,8,9]. Aneuploidy as a form of chromosome instability is a relevant factor in neurodegenerative changes in AD and in ageing [2,8,10,11,12,13] with reports that the number of aneuploid neurons in affected brain regions exceed 20% [14].…”

Section: Introductionmentioning

confidence: 99%

DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division

et al. 2013

Self Cite

View full text Add to dashboard Cite

While Alzheimer disease (AD) is considered a neurodegenerative disorder, the importance of chromosome instability in non-neuronal cells is equally important, not only for shedding light on the etiology of the disease, but also for possible diagnostic purposes and monitoring the progress of the disease. Here, we evaluated the frequency of DNA damage and expression of premature centromere division (PCD) in peripheral blood lymphocytes of sporadic AD patients, age-matched and young controls. The results show that in male patients with AD, the frequencies of PCD and DNA damage were significantly greater (88%, p < 0.01 and 38%, p < 0.05, respectively) than in age-matched control group. AD females had significantly increased frequency of PCD (134%, p < 0.01) as well as a higher frequency of DNA damage (37%, p < 0.05). Ageing per se, both in males and females, shows significant increase of percentages of PCD (2.3 times, p < 0.01 and 2.8 times, p < 0.01, respectively) and DNA damage (63%, p < 0.01 and 50%, p < 0.01, respectively) comparing with young controls. In addition, a strong (R² = 0.873, n = 6) and significant (p < 0.01) correlation between the frequencies of PCD and DNA damage was found in all examined groups. We may conclude that the increases in both parameters evaluated in this study are not only associated with normal ageing processes, but are markedly and significantly intensified in AD pathogenesis. Thus, our data support the view that AD is a generalized systemic disease, at least as for the increased DNA damage and PCD incidence in peripheral blood cells.

show abstract

Section: Introductionmentioning

confidence: 99%

DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Also, M phase markers: an increase of MPM 2 phosphoepitopes , Cdc 35A and B phosphatases and the findings of cell cycle phenotypes found as binucleation [114] and premature centromere division ''PCD'' [98,99,108] may result in abortive karyokinesis [115][116][117] found in AD.…”

Section: Resultsmentioning

confidence: 99%

“…This enables sister chromatide separation. This process has been altered in AD and has been seen as premature centromere division or PCD [98][99][100][101]. Moh, et al, [31] proposed that PCD occurrence expresses genome instability in which cell cycle re-entry takes place.…”

Section: Cohesin: the Postmitoic Genetic Switch?mentioning

confidence: 99%

“…This damage repair property is found to be tied to BRCA1 [105], a known DSB repair protein implicated in cancer [106] and AD [107]. The findings of cohesion instability or premature centromere division in peripheral cells [98,108] and in neuronal cells [99] of AD patients suggest that the secondary roles of cohesion are impaired [29,109]. A number of the proteins in the cohesin complex are associated with various diseases named ''cohesionapathies'' [110] suggesting that cohesin has roles in dividing and non-dividing cells other that chromosome regulation (Table 1).…”

Section: Cohesin: the Postmitoic Genetic Switch?mentioning

confidence: 99%

See 1 more Smart Citation

Late phase cell cycle proteins in Alzheimer’s disease: a possible target for therapy?

Bajić¹,

Bajić²,

Živković³

et al. 2016

J Syst Integr Neurosci

View full text Add to dashboard Cite

Alzheimer's disease (AD) is represented by neuronal loss and this loss is correlated to a constant state of neuronal instability induced by intrinsic and extrinsic factors. In this paper data is presented regarding the possible roles of late phase cell cycle proteins in normal and affected neurons with the goal that understanding the mechanisms involved in the regulation of these proteins may represent a novel strategy for AD treatment. The results demonstrate a relative differential pattern of expression of certain proteins (APC/C, Mad1 and Mad2, Bub R1, Bub1, CDK 11, cohesin subunit Rad 21 and astrin) in the AD brain versus age matched controls, and it is suggested that targeting these proteins might translate into potential treatments for AD. Although the data presented here is of some interest, the ability to translate such information into clinical applications is often a challenge.

show abstract

“…Moreover, PCD in specific chromosomes could also lead to apparent chromosomal gains in AD brain. 50 In any case, both aneuploid and tetraploid neurons seem to coexist in the AD brain.…”

Section: P75 Ntr As a Putative Trigger Of Neuronal Tetraploidy In Admentioning

confidence: 99%

A novel hypothesis for Alzheimer disease based on neuronal tetraploidy induced by p75^NTR

Frade

López-Sánchez²

2010

Cell Cycle

View full text Add to dashboard Cite

Premature centromere division of the X chromosome in neurons in Alzheimer’s disease

Abstract: Abbreviations used: AD, Alzheimer's disease; DAPI, diamindino phenylindole; FISH, fluorescent in situ hybridization; H&E, hematoxylin and eosin; PCD, premature centromere division; PCD,X, premature centromere division on the X chromosome.

Cited by 39 publications

References 59 publications

DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division

DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division

Late phase cell cycle proteins in Alzheimer’s disease: a possible target for therapy?

A novel hypothesis for Alzheimer disease based on neuronal tetraploidy induced by p75^NTR

Contact Info

Product

Resources

About

Premature centromere division of the X chromosome in neurons in Alzheimer’s disease

Abstract: Abbreviations used: AD, Alzheimer's disease; DAPI, diamindino phenylindole; FISH, fluorescent in situ hybridization; H&E, hematoxylin and eosin; PCD, premature centromere division; PCD,X, premature centromere division on the X chromosome.

Cited by 39 publications

References 59 publications

DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division

DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division

Late phase cell cycle proteins in Alzheimer’s disease: a possible target for therapy?

A novel hypothesis for Alzheimer disease based on neuronal tetraploidy induced by p75NTR

Contact Info

Product

Resources

About

A novel hypothesis for Alzheimer disease based on neuronal tetraploidy induced by p75^NTR