Brain transcriptomes of zebrafish and mouse Alzheimer's disease knock-in models imply early disrupted energy metabolism

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dc.contributor.authorBarthelson, K.
dc.contributor.authorNewman, M.
dc.contributor.authorLardelli, M.
dc.date.issued2022
dc.descriptionAccepted manuscript
dc.description.abstractEnergy production is the most fundamentally important cellular activity supporting all other functions, particularly in highly active organs such as brains, Here we summarise transcriptome analyses of young adult (pre-disease) brains from a collection of eleven early-onset familial Alzheimer’s disease (EOfAD)-like and non-EOfAD-like mutations in three zebrafish genes. The one cellular activity consistently predicted as affected by only the EOfAD-like mutations is oxidative phosphorylation that produces most of the brain’s energy. All the mutations were predicted to affect protein synthesis. We extended our analysis to knock-in mouse models of APOE alleles and found the same effect for the late onset Alzheimer’s disease risk allele 4. Our results support a common molecular basis for initiation of the pathological processes leading to both early and late onset forms of Alzheimer’s disease and illustrate the utility of zebrafish and of knock-in, single EOfAD mutation models for understanding the causes of this disease.
dc.description.statementofresponsibilityKarissa Barthelson, Morgan Newman, Michael Lardelli
dc.identifier.citationDisease Models and Mechanisms, 2022; 15(1):1-14
dc.identifier.doi10.1242/dmm.049187
dc.identifier.issn1754-8403
dc.identifier.issn1754-8411
dc.identifier.orcidBarthelson, K. [0000-0002-4693-8833]
dc.identifier.orcidNewman, M. [0000-0002-4930-4529]
dc.identifier.orcidLardelli, M. [0000-0002-4289-444X]
dc.identifier.urihttps://hdl.handle.net/2440/133838
dc.language.isoen
dc.publisherCompany of Biologists
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT1061006
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT1126422
dc.rights© 2021. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
dc.source.urihttps://doi.org/10.1242/dmm.049187
dc.subjectAlzheimer’s disease; zebrafish; mouse; RNA-seq; oxidative phosphorylation; brain
dc.titleBrain transcriptomes of zebrafish and mouse Alzheimer's disease knock-in models imply early disrupted energy metabolism
dc.typeJournal article
pubs.publication-statusPublished

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