| RRC ID |
73729
|
| 著者 |
Honda K, Saito Y, Saito H, Toyoda M, Abe R, Saito T, Saido TC, Michikawa M, Taru H, Sobu Y, Hata S, Nakaya T, Suzuki T.
|
| タイトル |
Accumulation of amyloid-β in the brain of mouse models of Alzheimer's disease is modified by altered gene expression in the presence of human apoE isoforms during aging.
|
| ジャーナル |
Neurobiol Aging
|
| Abstract |
Apolipoprotein E4 (apoE4) is a risk factor for Alzheimer's disease (AD). Here, we investigated brain amyloid-β (Aβ) accumulation throughout the aging process in an amyloid precursor protein (APP) knock-in (KI) mouse model of AD that expresses human APPNL-G-F with or without human apoE4 or apoE3. Brain Aβ42 levels were significantly lower in 9-month-old mice that express human isoforms of apoE than in age-matched APP-KI control mice. Linear accumulation of Aβ42 began in 5-month-old apoE4 mice, and a strong increase in Aβ42 levels was observed in 21-month-old apoE3 mice. Aβ42 levels in cerebroventricular fluid were higher in apoE3 than in apoE4 mice at 6-7 months of age, suggesting that apoE3 is more efficient at clearing Aβ42 than apoE4 at these ages. However, apoE3 protein levels were lower than apoE4 protein levels in the brains of 21-month-old apoE3 and apoE4 mice, respectively, which may explain the rapid increase in brain Aβ42 burden in apoE3 mice. We identified genes that were downregulated in a human apoE-dependent (apoE4 > apoE3) and age-dependent (apoE3 = apoE4) manner, which may regulate brain Aβ burden and/or AD progression. Analysis of gene expression in AD mouse models helps identify molecular mechanisms of pleiotropy by the human APOE gene during aging.
|
| 巻・号 |
123
|
| ページ |
63-74
|
| 公開日 |
2023-3-1
|
| DOI |
10.1016/j.neurobiolaging.2022.12.003
|
| PII |
S0197-4580(22)00257-3
|
| PMID |
36638682
|
| MeSH |
Aging / genetics
Aging / metabolism
Alzheimer Disease* / metabolism
Amyloid beta-Peptides / metabolism
Amyloid beta-Protein Precursor / genetics
Amyloid beta-Protein Precursor / metabolism
Animals
Apolipoprotein E3 / genetics
Apolipoprotein E3 / metabolism
Apolipoprotein E4 / genetics
Apolipoprotein E4 / metabolism
Apolipoproteins E / metabolism
Brain / metabolism
Gene Expression
Humans
Mice
Mice, Transgenic
Protein Isoforms / genetics
Protein Isoforms / metabolism
|
| IF |
4.347
|
| リソース情報 |
| 実験動物マウス |
RBRC06344
RBRC03390
RBRC03418 |
