| First Author | Barthelson K | Year | 2022 |
| Journal | Dis Model Mech | Volume | 15 |
| Issue | 1 | PubMed ID | 34842276 |
| Mgi Jnum | J:324405 | Mgi Id | MGI:6872269 |
| Doi | 10.1242/dmm.049187 | Citation | Barthelson K, et al. (2022) Brain transcriptomes of zebrafish and mouse Alzheimer's disease knock-in models imply early disrupted energy metabolism. Dis Model Mech 15(1):dmm049187 |
| abstractText | 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 epsilon4. 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. |
