| Literature DB >> 35418601 |
Andreas Giannisis1, Kalicharan Patra1, Anna K Edlund1, Lur Agirrezabala Nieto1, Joan Benedicto-Gras1, Simon Moussaud1, Andrés de la Rosa1, Daniel Twohig1, Tore Bengtsson2, Yuan Fu3, Guojun Bu3, Greg Bial4, Lander Foquet4, Christina Hammarstedt5, Stephen Strom5, Kristina Kannisto5, Jacob Raber6, Ewa Ellis7, Henrietta M Nielsen8.
Abstract
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 APOEε4, the strongest genetic AD risk factor, exhibit lower plasma apoE and altered brain integrity already at mid-life versus non-APOEε4 carriers. Whether altered plasma liver-derived apoE or specifically an APOEε4 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 ε4/ε4 versus an APOE ε2/ε3 genotype. Reduced endogenous mouse apoE levels in the brains of APOE ε4/ε4 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 APOEε4-associated risk of neurodegenerative disease.Entities:
Year: 2022 PMID： 35418601 DOI： 10.1038/s41380-022-01548-0
Source DB: PubMed Journal: Mol Psychiatry ISSN： 1359-4184 Impact factor: 13.437