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dc.contributor.author
Coskun, Pinar  
dc.contributor.author
Helguera, Pablo Rodolfo  
dc.contributor.author
Nemati, Zahra  
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Bohannan, Ryan C.  
dc.contributor.author
Thomas, Jean  
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Samuel, Schriner E.  
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Argueta, Jocelyn  
dc.contributor.author
Doran, Eric  
dc.contributor.author
Wallace, Douglas C.  
dc.contributor.author
Lott, Ira T.  
dc.contributor.author
Busciglio, Jorge  
dc.date.available
2019-05-16T18:11:37Z  
dc.date.issued
2016-08  
dc.identifier.citation
Coskun, Pinar; Helguera, Pablo Rodolfo; Nemati, Zahra; Bohannan, Ryan C.; Thomas, Jean; et al.; Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's Disease; IOS Press; Journal of Alzheimer's Disease; 55; 2; 8-2016; 737-748  
dc.identifier.issn
1387-2877  
dc.identifier.uri
http://hdl.handle.net/11336/76545  
dc.description.abstract
Deficits in mitochondrial function and oxidative stress play pivotal roles in Down syndrome (DS) and Alzheimer's disease (AD) and these alterations in mitochondria occur systemically in both conditions. Objective: We hypothesized that peripheral cells of elder subjects with DS exhibit disease-specific and dementia-specific metabolic features. To test this, we performed a comprehensive analysis of energy metabolism in lymphoblastic-cell-lines (LCLs) derived from subjects belonging to four groups: DS-with-dementia (DSAD), DS-without-dementia (DS), sporadic AD, and age-matched controls. Methods: LCLs were studied under regular or minimal feeding regimes with galactose or glucose as primary carbohydrate sources. We assessed metabolism under glycolysis or oxidative phosphorylation by quantifying cell viability, oxidative stress, ATP levels, mitochondrial membrane potential (MMP), mitochondrial calcium uptake, and autophagy. DS and DSAD LCLs showed slower growth rates under minimal feeding. DS LCLs mainly dependent on mitochondrial respiration exhibited significantly slower growth and higher levels of oxidative stress compared to other groups. While ATP levels (under mitochondrial inhibitors) and mitochondrial calcium uptake were significantly reduced in DSAD and AD cells, MMP was decreased in DS, DSAD, and AD LCLs. Finally, DS LCLs showed markedly reduced levels of the autophagy marker LC3-II, underscoring the close association between metabolic dysfunction and impaired autophagy in DS. Conclusion: There are significant mitochondrial functional changes in LCLs derived from DS, DSAD, and AD patients. Several parameters analyzed were consistently different between DS, DSAD, and AD lines suggesting that metabolic indicators between LCL groups may be utilized as biomarkers of disease progression and/or treatment outcomes.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
IOS Press  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Alzheimer'S Disease  
dc.subject
Autophagy  
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Dementia  
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Down Syndrome  
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Growth Retardation  
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Lymphoblastoid Cell Lines  
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Metabolic Alterations  
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Mitochondrial Dysfunction  
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Oxidative Stress  
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Inmunología  
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Medicina Básica  
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CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's Disease  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2019-04-15T18:14:14Z  
dc.journal.volume
55  
dc.journal.number
2  
dc.journal.pagination
737-748  
dc.journal.pais
Países Bajos  
dc.journal.ciudad
Amsterdam  
dc.description.fil
Fil: Coskun, Pinar. University of California at Irvine; Estados Unidos  
dc.description.fil
Fil: Helguera, Pablo Rodolfo. University of California at Irvine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina  
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Fil: Nemati, Zahra. University of California at Irvine; Estados Unidos  
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Fil: Bohannan, Ryan C.. University of California at Irvine; Estados Unidos  
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Fil: Thomas, Jean. University of California at Irvine; Estados Unidos  
dc.description.fil
Fil: Samuel, Schriner E.. University of California at Irvine; Estados Unidos  
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Fil: Argueta, Jocelyn. University of California at Irvine; Estados Unidos  
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Fil: Doran, Eric. University of California at Irvine; Estados Unidos  
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Fil: Wallace, Douglas C.. University of Pennsylvania; Estados Unidos  
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Fil: Lott, Ira T.. University of California at Irvine; Estados Unidos  
dc.description.fil
Fil: Busciglio, Jorge. University of California at Irvine; Estados Unidos  
dc.journal.title
Journal of Alzheimer's Disease  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.3233/JAD-160278  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/27802222