Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in Alzheimer's disease
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 conf...
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_19326203_v5_n4_p_GomezRavetti |
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paperaa:paper_19326203_v5_n4_p_GomezRavetti2023-06-12T16:51:27Z Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in Alzheimer's disease PLoS ONE 2010;5(4) Gómez Ravetti, M. Rosso, O.A. Berretta, R. Moscato, P. 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 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. 2010 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19326203_v5_n4_p_GomezRavetti |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| language |
Inglés |
| orig_language_str_mv |
eng |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
Artículo Artículo publishedVersion |
| author |
Gómez Ravetti, M. Rosso, O.A. Berretta, R. Moscato, P. |
| author_facet |
Gómez Ravetti, M. Rosso, O.A. Berretta, R. Moscato, P. |
| author_sort |
Gómez Ravetti, M. |
| title |
Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in Alzheimer's disease |
| title_short |
Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in Alzheimer's disease |
| title_full |
Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in Alzheimer's disease |
| title_fullStr |
Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in Alzheimer's disease |
| title_full_unstemmed |
Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in Alzheimer's disease |
| title_sort |
uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in alzheimer's disease |
| publishDate |
2010 |
| url |
http://hdl.handle.net/20.500.12110/paper_19326203_v5_n4_p_GomezRavetti |
| work_keys_str_mv |
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| _version_ |
1769810302145134592 |