Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/119731
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Type: Journal article
Title: Brain transcriptome analysis of a familial Alzheimer's disease-like mutation in the zebrafish presenilin 1 gene implies effects on energy production
Author: Newman, M.
Hin, N.
Pederson, S.
Lardelli, M.
Citation: Molecular Brain, 2019; 12(1):1-5
Publisher: Springer Nature; BioMed Central
Issue Date: 2019
ISSN: 1756-6606
1756-6606
Statement of
Responsibility: 
Morgan Newman, Nhi Hin, Stephen Pederson and Michael Lardelli
Abstract: To prevent or ameliorate Alzheimer's disease (AD) we must understand its molecular basis. AD develops over decades but detailed molecular analysis of AD brains is limited to postmortem tissue where the stresses initiating the disease may be obscured by compensatory responses and neurodegenerative processes. Rare, dominant mutations in a small number of genes, but particularly the gene PRESENILIN 1 (PSEN1), drive early onset of familial AD (EOfAD). Numerous transgenic models of AD have been constructed in mouse and other organisms, but transcriptomic analysis of these models has raised serious doubts regarding their representation of the disease state. Since we lack clarity regarding the molecular mechanism(s) underlying AD, we posit that the most valid approach is to model the human EOfAD genetic state as closely as possible. Therefore, we sought to analyse brains from zebrafish heterozygous for a single, EOfAD-like mutation in their PSEN1-orthologous gene, psen1. We previously introduced an EOfAD-like mutation (Q96_K97del) into the endogenous psen1 gene of zebrafish. Here, we analysed transcriptomes of young adult (6-month-old) entire brains from a family of heterozygous mutant and wild type sibling fish. Gene ontology (GO) analysis implies effects on mitochondria, particularly ATP synthesis, and on ATP-dependent processes including vacuolar acidification.
Keywords: Alzheimer’s disease; presenilin 1; mutation; transcriptome; brain; ATP synthesis; mitochondria; vacuolar acidification; zebrafish; genome editing
Rights: © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
RMID: 0030113851
DOI: 10.1186/s13041-019-0467-y
Grant ID: http://purl.org/au-research/grants/nhmrc/1061006
http://purl.org/au-research/grants/nhmrc/GNT1126422
Appears in Collections:Molecular and Biomedical Science publications

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