The Role of BMI1 in Late-Onset Sporadic Alzheimer’s Disease
Late-onset sporadic Alzheimer’s disease (LOAD) seems to contain a “hidden” component that cannot be explained by classical Mendelian genetics, with advanced aging being the strongest risk factor. More surprisingly, whole genome sequencing analyses of early-onset sporadic Alzheimer’s disease cohorts...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/11/7/825 |
| _version_ | 1797561793154908160 |
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| author | Ryan Hogan Anthony Flamier Eleonora Nardini Gilbert Bernier |
| author_facet | Ryan Hogan Anthony Flamier Eleonora Nardini Gilbert Bernier |
| author_sort | Ryan Hogan |
| collection | DOAJ |
| description | Late-onset sporadic Alzheimer’s disease (LOAD) seems to contain a “hidden” component that cannot be explained by classical Mendelian genetics, with advanced aging being the strongest risk factor. More surprisingly, whole genome sequencing analyses of early-onset sporadic Alzheimer’s disease cohorts also revealed that most patients do not present classical disease-associated variants or mutations. In this short review, we propose that <i>BMI1</i> is possibly epigenetically silenced in LOAD. Reduced <i>BMI1</i> expression is unique to LOAD compared to familial early-onset AD (EOAD) and other related neurodegenerative disorders; moreover, reduced expression of this single gene is sufficient to reproduce most LOAD pathologies in cellular and animal models. We also show the apparent amyloid and Tau-independent nature of this epigenetic alteration of <i>BMI1</i> expression. Lastly, examples of the mechanisms underlying epigenetic dysregulation of other LOAD-related genes are also illustrated. |
| first_indexed | 2024-03-10T18:19:40Z |
| format | Article |
| id | doaj.art-3aeedd2f478740459f0e10c967df6852 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T18:19:40Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-3aeedd2f478740459f0e10c967df68522023-11-20T07:24:40ZengMDPI AGGenes2073-44252020-07-0111782510.3390/genes11070825The Role of BMI1 in Late-Onset Sporadic Alzheimer’s DiseaseRyan Hogan0Anthony Flamier1Eleonora Nardini2Gilbert Bernier3Stem Cell and Developmental Biology Laboratory, Hôpital Maisonneuve-Rosemont, 5415 Boul. l’Assomption, Montreal, QC H1T 2M4, CanadaWhitehead Institute of Biomedical Research, 455 Main Street, Cambridge, MA 02142, USAWhitehead Institute of Biomedical Research, 455 Main Street, Cambridge, MA 02142, USAStem Cell and Developmental Biology Laboratory, Hôpital Maisonneuve-Rosemont, 5415 Boul. l’Assomption, Montreal, QC H1T 2M4, CanadaLate-onset sporadic Alzheimer’s disease (LOAD) seems to contain a “hidden” component that cannot be explained by classical Mendelian genetics, with advanced aging being the strongest risk factor. More surprisingly, whole genome sequencing analyses of early-onset sporadic Alzheimer’s disease cohorts also revealed that most patients do not present classical disease-associated variants or mutations. In this short review, we propose that <i>BMI1</i> is possibly epigenetically silenced in LOAD. Reduced <i>BMI1</i> expression is unique to LOAD compared to familial early-onset AD (EOAD) and other related neurodegenerative disorders; moreover, reduced expression of this single gene is sufficient to reproduce most LOAD pathologies in cellular and animal models. We also show the apparent amyloid and Tau-independent nature of this epigenetic alteration of <i>BMI1</i> expression. Lastly, examples of the mechanisms underlying epigenetic dysregulation of other LOAD-related genes are also illustrated.https://www.mdpi.com/2073-4425/11/7/825BMI1Alzheimer’s diseaselate-onsetsporadicepigenetics |
| spellingShingle | Ryan Hogan Anthony Flamier Eleonora Nardini Gilbert Bernier The Role of BMI1 in Late-Onset Sporadic Alzheimer’s Disease Genes BMI1 Alzheimer’s disease late-onset sporadic epigenetics |
| title | The Role of BMI1 in Late-Onset Sporadic Alzheimer’s Disease |
| title_full | The Role of BMI1 in Late-Onset Sporadic Alzheimer’s Disease |
| title_fullStr | The Role of BMI1 in Late-Onset Sporadic Alzheimer’s Disease |
| title_full_unstemmed | The Role of BMI1 in Late-Onset Sporadic Alzheimer’s Disease |
| title_short | The Role of BMI1 in Late-Onset Sporadic Alzheimer’s Disease |
| title_sort | role of bmi1 in late onset sporadic alzheimer s disease |
| topic | BMI1 Alzheimer’s disease late-onset sporadic epigenetics |
| url | https://www.mdpi.com/2073-4425/11/7/825 |
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