Beyond genetics: including the environmental dimension in amyloidosis mouse models for Alzheimer’s disease

Abstract

[...]generation knock-in mouse models, like AppNL−G−F mice, incorporated humanized sequences and clinical mutations within the mouse App gene, mitigating issues related to overexpression while still exhibiting Aβ accumulation. [...]peripheral inflammation has shown to decrease Aβ clearance via impaired microglial Aβ phagocytosis and an LRP-1 dependent decreased Aβ transport from brain to blood in addition to increased Aβ influx into the brain. [...]emerging evidence links AD to intestinal inflammation and altered gut microbiota as this may lead to gut barrier dysfunction, allowing the release of pro-inflammatory molecules and gut microbes into the periphery.