TY  - JOUR
AU  - Živković, Lada
AU  - Potparević, Biljana
AU  - Siedlak, Sandra L.
AU  - Perry, George
AU  - Plećaš-Solarović, Bosiljka
AU  - Milicević, Zorana
AU  - Bajić, Vladan
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1861
AB  - 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 lt 0.01 and 38%, p lt 0.05, respectively) than in age-matched control group. AD females had significantly increased frequency of PCD (134%, p lt 0.01) as well as a higher frequency of DNA damage (37%, p lt 0.05). Ageing per se, both in males and females, shows significant increase of percentages of PCD (2.3 times, p lt 0.01 and 2.8 times, p lt 0.01, respectively) and DNA damage (63%, p lt 0.01 and 50%, p lt 0.01, respectively) comparing with young controls. In addition, a strong (R-2 = 0.873, n = 6) and significant (p lt 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. copyright
PB  - Karger, Basel
T2  - Neurodegenerative Diseases
T1  - DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division
VL  - 12
IS  - 3
SP  - 156
EP  - 163
DO  - 10.1159/000346114
ER  - 

@article{
author = "Živković, Lada and Potparević, Biljana and Siedlak, Sandra L. and Perry, George and Plećaš-Solarović, Bosiljka and Milicević, Zorana and Bajić, Vladan",
year = "2013",
abstract = "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 lt 0.01 and 38%, p lt 0.05, respectively) than in age-matched control group. AD females had significantly increased frequency of PCD (134%, p lt 0.01) as well as a higher frequency of DNA damage (37%, p lt 0.05). Ageing per se, both in males and females, shows significant increase of percentages of PCD (2.3 times, p lt 0.01 and 2.8 times, p lt 0.01, respectively) and DNA damage (63%, p lt 0.01 and 50%, p lt 0.01, respectively) comparing with young controls. In addition, a strong (R-2 = 0.873, n = 6) and significant (p lt 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. copyright",
publisher = "Karger, Basel",
journal = "Neurodegenerative Diseases",
title = "DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division",
volume = "12",
number = "3",
pages = "156-163",
doi = "10.1159/000346114"
}

Živković, L., Potparević, B., Siedlak, S. L., Perry, G., Plećaš-Solarović, B., Milicević, Z.,& Bajić, V.. (2013). DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division. in Neurodegenerative Diseases
Karger, Basel., 12(3), 156-163.
https://doi.org/10.1159/000346114

Živković L, Potparević B, Siedlak SL, Perry G, Plećaš-Solarović B, Milicević Z, Bajić V. DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division. in Neurodegenerative Diseases. 2013;12(3):156-163.
doi:10.1159/000346114 .

Živković, Lada, Potparević, Biljana, Siedlak, Sandra L., Perry, George, Plećaš-Solarović, Bosiljka, Milicević, Zorana, Bajić, Vladan, "DNA Damage in Alzheimer Disease Lymphocytes and Its Relation to Premature Centromere Division" in Neurodegenerative Diseases, 12, no. 3 (2013):156-163,
https://doi.org/10.1159/000346114 . .

TY  - JOUR
AU  - Bajić, Vladan
AU  - Su, Bo
AU  - Lee, Hyoung-Gon
AU  - Kudo, Wataru
AU  - Siedlak, Sandra L.
AU  - Živković, Lada
AU  - Potparević, Biljana
AU  - Đelić, Ninoslav
AU  - Milicević, Zorana
AU  - Singh, Avneet K.
AU  - Fahmy, Lara M.
AU  - Wang, Xinglong
AU  - Smith, Mark A.
AU  - Zhu, Xiongwei
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1554
AB  - Post-mitotic neurons are typically terminally differentiated and in a quiescent status. However, in Alzheimer disease (AD), many neurons display ectopic re-expression of cell cycle-related proteins. Cyclin-dependent kinase 11 (CDK11) mRNA produces a 110-kDa protein (CDK11(p110)) throughout the cell cycle, a 58-kDa protein (CDK11(p58)) that is specifically translated from an internal ribosome entry site and expressed only in the G(2)/M phase of the cell cycle, and a 46-kDa protein (CDK11(p46)) that is considered to be apoptosis specific. CDK11 is required for sister chromatid cohesion and the completion of mitosis. In this study, we found that the expression patterns of CDK11 vary such that cytoplasmic CDK11 is increased in AD cellular processes, compared to a pronounced nuclear expression pattern in most controls. We also investigated the effect of amyloid precursor protein (APP) on CDK11 expression in vitro by using M17 cells overexpressing wild-type APP and APP Swedish mutant phenotype and found increased CDK11 expression compared to empty vector. In addition, amyloid-beta(25-35) resulted in increased CDK11 in M17 cells. These data suggest that CDK11 may play a vital role in cell cycle re-entry in AD neurons in an APP-dependent manner, thus presenting an intriguing novel function of the APP signaling pathway in AD.
PB  - BMC, LONDON
T2  - Cellular & Molecular Biology Letters
T1  - Mislocalization of CDK11/PITSLRE, a regulator of the G2/M phase of the cell cycle, in Alzheimer disease
VL  - 16
IS  - 3
SP  - 359
EP  - 372
DO  - 10.2478/s11658-011-0011-2
ER  - 

@article{
author = "Bajić, Vladan and Su, Bo and Lee, Hyoung-Gon and Kudo, Wataru and Siedlak, Sandra L. and Živković, Lada and Potparević, Biljana and Đelić, Ninoslav and Milicević, Zorana and Singh, Avneet K. and Fahmy, Lara M. and Wang, Xinglong and Smith, Mark A. and Zhu, Xiongwei",
year = "2011",
abstract = "Post-mitotic neurons are typically terminally differentiated and in a quiescent status. However, in Alzheimer disease (AD), many neurons display ectopic re-expression of cell cycle-related proteins. Cyclin-dependent kinase 11 (CDK11) mRNA produces a 110-kDa protein (CDK11(p110)) throughout the cell cycle, a 58-kDa protein (CDK11(p58)) that is specifically translated from an internal ribosome entry site and expressed only in the G(2)/M phase of the cell cycle, and a 46-kDa protein (CDK11(p46)) that is considered to be apoptosis specific. CDK11 is required for sister chromatid cohesion and the completion of mitosis. In this study, we found that the expression patterns of CDK11 vary such that cytoplasmic CDK11 is increased in AD cellular processes, compared to a pronounced nuclear expression pattern in most controls. We also investigated the effect of amyloid precursor protein (APP) on CDK11 expression in vitro by using M17 cells overexpressing wild-type APP and APP Swedish mutant phenotype and found increased CDK11 expression compared to empty vector. In addition, amyloid-beta(25-35) resulted in increased CDK11 in M17 cells. These data suggest that CDK11 may play a vital role in cell cycle re-entry in AD neurons in an APP-dependent manner, thus presenting an intriguing novel function of the APP signaling pathway in AD.",
publisher = "BMC, LONDON",
journal = "Cellular & Molecular Biology Letters",
title = "Mislocalization of CDK11/PITSLRE, a regulator of the G2/M phase of the cell cycle, in Alzheimer disease",
volume = "16",
number = "3",
pages = "359-372",
doi = "10.2478/s11658-011-0011-2"
}

Bajić, V., Su, B., Lee, H., Kudo, W., Siedlak, S. L., Živković, L., Potparević, B., Đelić, N., Milicević, Z., Singh, A. K., Fahmy, L. M., Wang, X., Smith, M. A.,& Zhu, X.. (2011). Mislocalization of CDK11/PITSLRE, a regulator of the G2/M phase of the cell cycle, in Alzheimer disease. in Cellular & Molecular Biology Letters
BMC, LONDON., 16(3), 359-372.
https://doi.org/10.2478/s11658-011-0011-2

Bajić V, Su B, Lee H, Kudo W, Siedlak SL, Živković L, Potparević B, Đelić N, Milicević Z, Singh AK, Fahmy LM, Wang X, Smith MA, Zhu X. Mislocalization of CDK11/PITSLRE, a regulator of the G2/M phase of the cell cycle, in Alzheimer disease. in Cellular & Molecular Biology Letters. 2011;16(3):359-372.
doi:10.2478/s11658-011-0011-2 .

Bajić, Vladan, Su, Bo, Lee, Hyoung-Gon, Kudo, Wataru, Siedlak, Sandra L., Živković, Lada, Potparević, Biljana, Đelić, Ninoslav, Milicević, Zorana, Singh, Avneet K., Fahmy, Lara M., Wang, Xinglong, Smith, Mark A., Zhu, Xiongwei, "Mislocalization of CDK11/PITSLRE, a regulator of the G2/M phase of the cell cycle, in Alzheimer disease" in Cellular & Molecular Biology Letters, 16, no. 3 (2011):359-372,
https://doi.org/10.2478/s11658-011-0011-2 . .

TY  - JOUR
AU  - Živković, Lada
AU  - Potparević, Biljana
AU  - Plećaš-Solarović, Bosiljka
AU  - Đelić, Ninoslav
AU  - Ocić, Gordana
AU  - Smiljković, Predrag
AU  - Siedlak, Sandra L.
AU  - Smith, Mark A.
AU  - Bajić, Vladan
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1370
AB  - Chromosomal alterations are a feature of both aging and Alzheimer's disease (AD). This study examined if premature centromere division (PCD), a chromosomal instability indicator increased in AD, is correlated with aging or, instead, represents a de novo chromosomal alteration due to accelerating aging in AD. PCD in peripheral blood lymphocytes was determined in sporadic AD patients and gender and age-matched unaffected controls. Metaphase nuclei were analyzed for chromosomes showing PCD, X chromosomes with PCD (PCD,X), and acrocentric chromosomes showing PCD. AD patients, regardless of age, demonstrated increased PCD on any chromosome and PCD on acrocentric chromosomes in both genders, whereas an increase in frequency of PCD,X was expressed only in women. This cytogenetic analysis suggests that PCD is a feature of AD, rather than an epiphenomenon of chronological aging, and may be useful as a physiological biomarker that can be used for disease diagnosis.
PB  - Oxford Univ Press Inc, Cary
T2  - Journals of Gerontology Series A: Biological Sciences and Medical Sciences
T1  - Premature Centromere Division of Metaphase Chromosomes in Peripheral Blood Lymphocytes of Alzheimer's Disease Patients: Relation to Gender and Age
VL  - 65
IS  - 12
SP  - 1269
EP  - 1274
DO  - 10.1093/gerona/glq148
ER  - 

@article{
author = "Živković, Lada and Potparević, Biljana and Plećaš-Solarović, Bosiljka and Đelić, Ninoslav and Ocić, Gordana and Smiljković, Predrag and Siedlak, Sandra L. and Smith, Mark A. and Bajić, Vladan",
year = "2010",
abstract = "Chromosomal alterations are a feature of both aging and Alzheimer's disease (AD). This study examined if premature centromere division (PCD), a chromosomal instability indicator increased in AD, is correlated with aging or, instead, represents a de novo chromosomal alteration due to accelerating aging in AD. PCD in peripheral blood lymphocytes was determined in sporadic AD patients and gender and age-matched unaffected controls. Metaphase nuclei were analyzed for chromosomes showing PCD, X chromosomes with PCD (PCD,X), and acrocentric chromosomes showing PCD. AD patients, regardless of age, demonstrated increased PCD on any chromosome and PCD on acrocentric chromosomes in both genders, whereas an increase in frequency of PCD,X was expressed only in women. This cytogenetic analysis suggests that PCD is a feature of AD, rather than an epiphenomenon of chronological aging, and may be useful as a physiological biomarker that can be used for disease diagnosis.",
publisher = "Oxford Univ Press Inc, Cary",
journal = "Journals of Gerontology Series A: Biological Sciences and Medical Sciences",
title = "Premature Centromere Division of Metaphase Chromosomes in Peripheral Blood Lymphocytes of Alzheimer's Disease Patients: Relation to Gender and Age",
volume = "65",
number = "12",
pages = "1269-1274",
doi = "10.1093/gerona/glq148"
}

Živković, L., Potparević, B., Plećaš-Solarović, B., Đelić, N., Ocić, G., Smiljković, P., Siedlak, S. L., Smith, M. A.,& Bajić, V.. (2010). Premature Centromere Division of Metaphase Chromosomes in Peripheral Blood Lymphocytes of Alzheimer's Disease Patients: Relation to Gender and Age. in Journals of Gerontology Series A: Biological Sciences and Medical Sciences
Oxford Univ Press Inc, Cary., 65(12), 1269-1274.
https://doi.org/10.1093/gerona/glq148

Živković L, Potparević B, Plećaš-Solarović B, Đelić N, Ocić G, Smiljković P, Siedlak SL, Smith MA, Bajić V. Premature Centromere Division of Metaphase Chromosomes in Peripheral Blood Lymphocytes of Alzheimer's Disease Patients: Relation to Gender and Age. in Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2010;65(12):1269-1274.
doi:10.1093/gerona/glq148 .

Živković, Lada, Potparević, Biljana, Plećaš-Solarović, Bosiljka, Đelić, Ninoslav, Ocić, Gordana, Smiljković, Predrag, Siedlak, Sandra L., Smith, Mark A., Bajić, Vladan, "Premature Centromere Division of Metaphase Chromosomes in Peripheral Blood Lymphocytes of Alzheimer's Disease Patients: Relation to Gender and Age" in Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 65, no. 12 (2010):1269-1274,
https://doi.org/10.1093/gerona/glq148 . .

TY  - JOUR
AU  - Bajić, Vladan
AU  - Potparević, Biljana
AU  - Živković, Lada
AU  - Bonda, David J.
AU  - Siedlak, Sandra L.
AU  - Casadesus, Gemma
AU  - Lee, Hyoung-Gon
AU  - Smith, Mark A.
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1212
AB  - 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 accelarated aging of the affected brain.
PB  - Churchill Livingstone, Edinburgh
T2  - Medical Hypotheses
T1  - The X-chromosome instability phenotype in Alzheimer's disease: A clinical sign of accelerating aging?
VL  - 73
IS  - 6
SP  - 917
EP  - 920
DO  - 10.1016/j.mehy.2009.06.046
ER  - 

@article{
author = "Bajić, Vladan and Potparević, Biljana and Živković, Lada and Bonda, David J. and Siedlak, Sandra L. and Casadesus, Gemma and Lee, Hyoung-Gon and Smith, Mark A.",
year = "2009",
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 accelarated aging of the affected brain.",
publisher = "Churchill Livingstone, Edinburgh",
journal = "Medical Hypotheses",
title = "The X-chromosome instability phenotype in Alzheimer's disease: A clinical sign of accelerating aging?",
volume = "73",
number = "6",
pages = "917-920",
doi = "10.1016/j.mehy.2009.06.046"
}

Bajić, V., Potparević, B., Živković, L., Bonda, D. J., Siedlak, S. L., Casadesus, G., Lee, H.,& Smith, M. A.. (2009). The X-chromosome instability phenotype in Alzheimer's disease: A clinical sign of accelerating aging?. in Medical Hypotheses
Churchill Livingstone, Edinburgh., 73(6), 917-920.
https://doi.org/10.1016/j.mehy.2009.06.046

Bajić V, Potparević B, Živković L, Bonda DJ, Siedlak SL, Casadesus G, Lee H, Smith MA. The X-chromosome instability phenotype in Alzheimer's disease: A clinical sign of accelerating aging?. in Medical Hypotheses. 2009;73(6):917-920.
doi:10.1016/j.mehy.2009.06.046 .

Bajić, Vladan, Potparević, Biljana, Živković, Lada, Bonda, David J., Siedlak, Sandra L., Casadesus, Gemma, Lee, Hyoung-Gon, Smith, Mark A., "The X-chromosome instability phenotype in Alzheimer's disease: A clinical sign of accelerating aging?" in Medical Hypotheses, 73, no. 6 (2009):917-920,
https://doi.org/10.1016/j.mehy.2009.06.046 . .