| First Author | Giannisis A | Year | 2022 |
| Journal | Mol Psychiatry | Volume | 27 |
| Issue | 8 | Pages | 3533-3543 |
| PubMed ID | 35418601 | Mgi Jnum | J:334990 |
| Mgi Id | MGI:7464982 | Doi | 10.1038/s41380-022-01548-0 |
| Citation | Giannisis A, et al. (2022) Brain integrity is altered by hepatic APOE epsilon4 in humanized-liver mice. Mol Psychiatry 27(8):3533-3543 |
| abstractText | Liver-generated plasma apolipoprotein E (apoE) does not enter the brain but nonetheless correlates with Alzheimer's disease (AD) risk and AD biomarker levels. Carriers of APOEepsilon4, the strongest genetic AD risk factor, exhibit lower plasma apoE and altered brain integrity already at mid-life versus non-APOEepsilon4 carriers. Whether altered plasma liver-derived apoE or specifically an APOEepsilon4 liver phenotype promotes neurodegeneration is unknown. Here we investigated the brains of Fah-/-, Rag2-/-, Il2rg-/- mice on the Non-Obese Diabetic (NOD) background (FRGN) with humanized-livers of an AD risk-associated APOE epsilon4/epsilon4 versus an APOE epsilon2/epsilon3 genotype. Reduced endogenous mouse apoE levels in the brains of APOE epsilon4/epsilon4 liver mice were accompanied by various changes in markers of synaptic integrity, neuroinflammation and insulin signaling. Plasma apoE4 levels were associated with unfavorable changes in several of the assessed markers. These results propose a previously unexplored role of the liver in the APOEepsilon4-associated risk of neurodegenerative disease. |
