| 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
|
| Resource |
| Mice |
RBRC03390
RBRC03418
RBRC06344 |
