Female-specific risk of Alzheimer's disease is associated with tau phosphorylation processes: a transcriptome-wide interaction analysis

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• dc.contributor.author Cáceres, Alejandro
• dc.contributor.author González Ruiz, Juan Ramón
• dc.date.accessioned 2021-04-20T06:21:10Z
• dc.date.issued 2020
• dc.description.abstract The levels of tau phosphorylation differ between sexes in Alzheimer's disease (AD). Transcriptome-wide associations of sex by disease interaction could indicate whether specific genes underlie sex differences in tau pathology; however, no such study has been reported yet. We report the first analysis of the effect of the interaction between disease status and sex on differential gene expression, meta-analyzing transcriptomic data from the 3 largest publicly available case-control studies (N = 785) in the brain to date. A total of 128 genes, significantly associated with sex-AD interactions, were enriched in phosphoproteins (false discovery rate (FDR) = 0.001). High and consistent associations were found for the overexpressions of NCL (FDR = 0.002), whose phosphorylated protein generates an epitope against neurofibrillary tangles and KIF2A (FDR = 0.005), a microtubule-associated motor protein gene. Transcriptome-wide interaction analyses suggest sex-modulated tau phosphorylation, at sites like Thr231, Ser199, or Ser202 that could increase the risk of women to AD and indicate sex-specific strategies for intervention and prevention.
• dc.description.sponsorship This research has received funding from the Spanish Ministry of Education, Innovation and Universities, the National Agency for Research, the Fund for Regional Development (RTI2018-100789-B-I00) and the Catalan Department of Economy and Knowledge (SGR2017/801) and the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S)
• dc.format.mimetype application/pdf
• dc.identifier.citation Cáceres A, González JR. Female-specific risk of Alzheimer's disease is associated with tau phosphorylation processes: a transcriptome-wide interaction analysis. Neurobiol Aging. 2020 Dec; 96: 104-108. DOI: 10.1016/j.neurobiolaging.2020.08.020
• dc.identifier.doi http://dx.doi.org/10.1016/j.neurobiolaging.2020.08.020
• dc.identifier.issn 0197-4580
• dc.identifier.uri http://hdl.handle.net/10230/47150
• dc.language.iso eng
• dc.publisher Elsevier
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.neurobiolaging.2020.08.020
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Alzheimer, Malaltia d'
• dc.subject.other Dones malaltes mentals
• dc.subject.other Genètica
• dc.subject.other Fosfoproteïnes
• dc.title Female-specific risk of Alzheimer's disease is associated with tau phosphorylation processes: a transcriptome-wide interaction analysis
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion