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Abstract:

Background: Alzheimer's disease (AD) is characterized by a neurodegenerative progression that alters cognition. On a phenotypical level, cognition is evaluated by means of the MiniMental State Examination (MMSE) and the post-morten examination of Neurofibrillary Tangle count (NFT) helps to confirm an AD diagnostic. The MMSE evaluates different aspects of cognition including orientation, short-term memory (retention and recall), attention and language. As there is a normal cognitive decline with aging, and death is the final state on which NFT can be counted, the identification of brain gene expression biomarkers from these phenotypical measures has been elusive. Methodology/Principal Findings: We have reanalysed a microarray dataset contributed in 2004 by Blalock et al. of 31 samples corresponding to hippocampus gene expression from 22 AD subjects of varying degree of severity and 9 controls. Instead of only relying on correlations of gene expression with the associated MMSE and NFT measures, and by using modern bioinformatics methods based on information theory and combinatorial optimization, we uncovered a 1,372-probe gene expression signature that presents a high-consensus with established markers of progression in AD. The signature reveals alterations in calcium, insulin, phosphatidylinositol and wnt-signalling. Among the most correlated gene probes with AD severity we found those linked to synaptic function, neurofilament bundle assembly and neuronal plasticity. Conclusions/Significance: A transcription factors analysis of 1,372-probe signature reveals significant associations with the EGR/KROX family of proteins, MAZ, and E2F1. The gene homologous of EGR1, zif268, Egr-1 or Zenk, together with other members of the EGR family, are consolidating a key role in the neuronal plasticity in the brain. These results indicate a degree of commonality between putative genes involved in AD and prion-induced neurodegenerative processes that warrants further investigation. © 2010 Go ́mez Ravetti et al.

Registro:

Documento: Artículo
Título:Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in Alzheimer's disease
Autor:Gómez Ravetti, M.; Rosso, O.A.; Berretta, R.; Moscato, P.
Filiación:Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, The University of Newcastle, Callaghan, NSW, Australia
Hunter Medical Research Institute, Information Based Medicine Program, John Hunter Hospital, New Lambton Heights, NSW, Australia
Australian Research Council Centre of Excellence in Bioinformatics, Callaghan, NSW, Australia
Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, Argentina
Palabras clave:biological marker; calcium; early growth response factor; epidermal growth factor receptor; insulin; Myc associated zinc finger protein; phosphatidylinositol; transcription factor; transcription factor E2F1; unclassified drug; Wnt protein; zinc finger protein; Alzheimer disease; article; bioinformatics; calcium signaling; clinical article; cognitive defect; controlled study; disease course; disease severity; gene expression profiling; gene expression regulation; gene probe; hippocampus; human; human tissue; information science; microarray analysis; mini mental state examination; nerve cell plasticity; neurofibrillary tangle; neurofilament; sequence homology; signal transduction; Alzheimer Disease; Biological Markers; Cognition Disorders; Computational Biology; Gene Expression Profiling; Hippocampus; Humans; Neuronal Plasticity; Oligonucleotide Array Sequence Analysis; Transcription Factors
Año:2010
Volumen:5
Número:4
DOI: http://dx.doi.org/10.1371/journal.pone.0010153
Título revista:PLoS ONE
Título revista abreviado:PLoS ONE
ISSN:19326203
CAS:calcium, 14092-94-5, 7440-70-2; epidermal growth factor receptor, 79079-06-4; insulin, 9004-10-8; Biological Markers; Transcription Factors
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_19326203_v5_n4_p_GomezRavetti.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v5_n4_p_GomezRavetti

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Citas:

---------- APA ----------
Gómez Ravetti, M., Rosso, O.A., Berretta, R. & Moscato, P. (2010) . Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in Alzheimer's disease. PLoS ONE, 5(4).
http://dx.doi.org/10.1371/journal.pone.0010153
---------- CHICAGO ----------
Gómez Ravetti, M., Rosso, O.A., Berretta, R., Moscato, P. "Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in Alzheimer's disease" . PLoS ONE 5, no. 4 (2010).
http://dx.doi.org/10.1371/journal.pone.0010153
---------- MLA ----------
Gómez Ravetti, M., Rosso, O.A., Berretta, R., Moscato, P. "Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in Alzheimer's disease" . PLoS ONE, vol. 5, no. 4, 2010.
http://dx.doi.org/10.1371/journal.pone.0010153
---------- VANCOUVER ----------
Gómez Ravetti, M., Rosso, O.A., Berretta, R., Moscato, P. Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in Alzheimer's disease. PLoS ONE. 2010;5(4).
http://dx.doi.org/10.1371/journal.pone.0010153