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

Disease Models & Mechanisms

Michael Lardelli¹  Karissa Barthelson¹  Morgan Newman¹ 

[1] Alzheimer's Disease Genetics Laboratory, School of Biological Sciences, University of Adelaide, North Terrace, Adelaide, SA 5005, Australia;

关键词: alzheimer's disease;    zebrafish;    mouse;    rna-seq;    oxidative phosphorylation;    brain;   

DOI  :  10.1242/dmm.049187

来源: DOAJ

【 摘 要 】

Energy 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 11 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, which produces most of the energy of the brain. 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 ε4. Our results support a common molecular basis for the initiation of the pathological processes leading to both early and late onset forms of Alzheimer's disease, and illustrate the utility of zebrafish and knock-in single EOFAD mutation models for understanding the causes of this disease.

【 授权许可】

Unknown