A decade progress in the phenotyping of AppNL-G-F knock-in mouse model of Alzheimer’s disease

Abstract

Numerous mouse models of Alzheimer’s disease (AD) have developed since the discovery of mutations causing familial AD. These models successfully recapitulate the progressive amyloid pathology over time, thus serving as indispensable tools for improving our understanding of the pathogenesis. However, there is a growing concern about artificial phenotypes in these transgenic mouse models, resulting from overexpression of mutant amyloid precursor protein (APP) under artificial promoters. To address this issue, App knock-in (KI) mice were developed to produce mutated human β-amyloid (Aβ) from the endogenous App locus. Since the first characterisation in 2014, gathering evidence has made significant progress in the phenotype analysis of this mouse model. Here, we provide an update on novel phenotypes observed in App^NL-G-F KI mice. In particular, we will highlight how the progression of amyloid pathology is related to neuronal pathology, behavioural phenotype, and microglial response.