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Inhibitor of DNA Binding Protein 3 (ID3) and Nuclear Respiratory Factor 1 (NRF1) Mediated Transcriptional Gene Signatures are Associated with the Severity of Cerebral Amyloid Angiopathy.
- Source :
-
Molecular neurobiology [Mol Neurobiol] 2024 Feb; Vol. 61 (2), pp. 835-882. Date of Electronic Publication: 2023 Sep 05. - Publication Year :
- 2024
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Abstract
- Cerebral amyloid angiopathy (CAA) is a degenerative vasculopathy. We have previously shown that transcription regulating proteins- inhibitor of DNA binding protein 3 (ID3) and the nuclear respiratory factor 1 (NRF1) contribute to vascular dysregulation. In this study, we have identified sex specific ID3 and NRF1-mediated gene networks in CAA patients diagnosed with Alzheimer's Disease (AD). High expression of ID3 mRNA coupled with low NRF1 mRNA levels was observed in the temporal cortex of men and women CAA patients. Low NRF1 mRNA expression in the temporal cortex was found in men with severe CAA. High ID3 expression was found in women with the genetic risk factor APOE4. Low NRF1 expression was also associated with APOE4 in women with CAA. Genome wide transcriptional activity of both ID3 and NRF1 paralleled their mRNA expression levels. Sex specific differences in transcriptional gene signatures of both ID3 and NRF1 were observed. These findings were further corroborated by Bayesian machine learning and the GeNIe simulation models. Dynamic machine learning using a Monte Carlo Markov Chain (MCMC) gene ordering approach revealed that ID3 was associated with disease severity in women. NRF1 was associated with CAA and severity of this disease in men. These findings suggest that aberrant ID3 and NRF1 activity presumably plays a major role in the pathogenesis and severity of CAA. Further analyses of ID3- and NRF1-regulated molecular drivers of CAA may provide new targets for personalized medicine and/or prevention strategies against CAA.<br /> (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Female
Humans
Male
Amyloid beta-Peptides metabolism
Apolipoprotein E4
Bayes Theorem
DNA-Binding Proteins
Inhibitor of Differentiation Proteins
Neoplasm Proteins
Nuclear Respiratory Factor 1 genetics
RNA, Messenger genetics
Alzheimer Disease pathology
Cerebral Amyloid Angiopathy complications
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1182
- Volume :
- 61
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 37668961
- Full Text :
- https://doi.org/10.1007/s12035-023-03541-2