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dc.contributor.authorPellegrini, C.
dc.contributor.authorFernandes Durso, Danielle
dc.contributor.authorBacalini, Maria Giulia
dc.date2022-08-11T08:08:26.000
dc.date.accessioned2022-08-23T15:55:01Z
dc.date.available2022-08-23T15:55:01Z
dc.date.issued2020-12-02
dc.date.submitted2021-01-14
dc.identifier.citation<p>medRxiv 2020.11.25.20238360; doi: https://doi.org/10.1101/2020.11.25.20238360. <a href="https://doi.org/10.1101/2020.11.25.20238360" target="_blank" title="preprint in medRxiv">Link to preprint on medRxiv.</a></p>
dc.identifier.doi10.1101/2020.11.25.20238360
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29662
dc.description<p>This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.</p> <p>Full author list omitted for brevity. For the full list of authors, see article.</p>
dc.description.abstractAlzheimer’s disease (AD) is characterized by specific alterations of brain DNA methylation (DNAm) patterns. Age and sex, two major risk factors for AD, are also known to largely affect the epigenetic profiles in the brain, but their contribution to AD-associated DNAm changes has been poorly investigated. In this study we considered publicly available DNAm datasets of 4 brain regions (temporal, frontal, entorhinal cortex and cerebellum) from healthy adult subjects and AD patients, and performed a meta-analysis to identify sex-, age- and AD-associated epigenetic profiles. We showed that DNAm differences between males and females tend to be shared between the 4 brain regions, while aging differently affects cortical regions compared to cerebellum. We found that the proportion of sex-dependent probes whose methylation changes also during aging is higher than expected, but that differences between males and females tend to be maintained, with only few probes showing sex-by-age interaction. We did not find significant overlaps between AD- and sex-associated probes, nor disease-by-sex interaction effects. On the contrary, we found that AD-related epigenetic modifications are significantly enriched in probes whose DNAm changes with age and that there is a high concordance between the direction of changes (hyper or hypo-methylation) in aging and AD, supporting accelerated epigenetic aging in the disease. In conclusion, we demonstrated that age-associated, but not sex-associated DNAm concurs to the epigenetic deregulation observed in AD, providing new insight on how advanced age enables neurodegeneration.
dc.language.isoen_US
dc.rightsThe copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectGenetic and Genomic Medicine
dc.subjectAlzheimer’s disease
dc.subjectaging
dc.subjectsex
dc.subjectbrain
dc.subjectepigenetic profiles
dc.subjectneurodegeneration
dc.subjectepigenetic modifications
dc.subjectDNA methylation
dc.subjectGenetics and Genomics
dc.subjectGeriatrics
dc.subjectNervous System
dc.subjectNervous System Diseases
dc.subjectNeuroscience and Neurobiology
dc.subjectPsychiatry and Psychology
dc.titleA meta-analysis of brain DNA methylation across sex, age and Alzheimer’s disease points for accelerated epigenetic aging in neurodegeneration [preprint]
dc.typePreprint
dc.source.journaltitlemedRxiv
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2885&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1877
dc.identifier.contextkey21085137
refterms.dateFOA2022-08-23T15:55:01Z
html.description.abstract<p><p id="x-x-x-x-x-x-p-2">Alzheimer’s disease (AD) is characterized by specific alterations of brain DNA methylation (DNAm) patterns. Age and sex, two major risk factors for AD, are also known to largely affect the epigenetic profiles in the brain, but their contribution to AD-associated DNAm changes has been poorly investigated. In this study we considered publicly available DNAm datasets of 4 brain regions (temporal, frontal, entorhinal cortex and cerebellum) from healthy adult subjects and AD patients, and performed a meta-analysis to identify sex-, age- and AD-associated epigenetic profiles. We showed that DNAm differences between males and females tend to be shared between the 4 brain regions, while aging differently affects cortical regions compared to cerebellum. We found that the proportion of sex-dependent probes whose methylation changes also during aging is higher than expected, but that differences between males and females tend to be maintained, with only few probes showing sex-by-age interaction. We did not find significant overlaps between AD- and sex-associated probes, nor disease-by-sex interaction effects. On the contrary, we found that AD-related epigenetic modifications are significantly enriched in probes whose DNAm changes with age and that there is a high concordance between the direction of changes (hyper or hypo-methylation) in aging and AD, supporting accelerated epigenetic aging in the disease.</p> <p>In conclusion, we demonstrated that age-associated, but not sex-associated DNAm concurs to the epigenetic deregulation observed in AD, providing new insight on how advanced age enables neurodegeneration.</p>
dc.identifier.submissionpathfaculty_pubs/1877
dc.contributor.departmentWellstone Center for FSHD
dc.contributor.departmentDepartment of Neurology


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The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Except where otherwise noted, this item's license is described as The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.