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

Karissa Barthelson, Morgan Newman, Michael Lardelli

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Abstract

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 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 ε4. 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.

Original languageEnglish
Article numberdmm049187
Number of pages14
JournalDMM Disease Models and Mechanisms
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 2022
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Brain
  • Mouse
  • Oxidative phosphorylation
  • RNA-seq
  • Zebrafish

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