RRC ID 77867
Author Takebayashi Y, Yamazaki Y, Yamada H, Yazawa K, Nakamori M, Kurashige T, Morino H, Takahashi T, Sotomaru Y, Maruyama H.
Title Apolipoprotein E genotype-dependent accumulation of amyloid β in APP-knock-in mouse model of Alzheimer's disease.
Journal Biochem Biophys Res Commun
Abstract Apolipoprotein E4 (APOE4), the strongest risk factor for late-onset Alzheimer's disease (AD), has been revealed to cause greater accumulation of extracellular amyloid β (Aβ) aggregates than does APOE3 in traditional transgenic mouse models of AD. However, concerns that the overexpression paradigm might have affected the phenotype remain. Amyloid precursor protein (APP)-knock-in (KI) mice, incorporating APP mutations associated with AD development, offer an alternative approach for overproducing pathogenic Aβ without needing overexpression of APP. Here, we present the results of comprehensive analyses of pathological and biochemical traits in the brains of APP-KI mice harboring APP-associated familial AD mutations (APPNL-G-F/NL-G-F mice) crossed with human APOE-KI mice. Immunohistochemical and biochemical analyses revealed the APOE genotype-dependent increase in Aβ pathology and glial activation, which was evident within 8 months in the mouse model. These results suggested that this mouse model may be valuable for investigating APOE pathobiology within a reasonable experimental time frame. Thus, this model can be considered in investigating the interaction between APOE and Aβ in vivo, which may not be addressed appropriately by using other transgenic mouse models.
Volume 683
Pages 149106
Published 2023-11-26
DOI 10.1016/j.bbrc.2023.10.038
PII S0006-291X(23)01190-7
PMID 37857162
MeSH Alzheimer Disease* / metabolism Amyloid beta-Peptides / metabolism Amyloid beta-Protein Precursor / genetics Amyloid beta-Protein Precursor / metabolism Animals Apolipoprotein E3 / genetics Apolipoproteins E / genetics Disease Models, Animal Genotype Humans Mice Mice, Transgenic
IF 2.985
Mice RBRC03390 RBRC03418 RBRC06344