| First Author | Honda K | Year | 2023 |
| Journal | Neurobiol Aging | Volume | 123 |
| Pages | 63-74 | PubMed ID | 36638682 |
| Mgi Jnum | J:332909 | Mgi Id | MGI:7430589 |
| Doi | 10.1016/j.neurobiolaging.2022.12.003 | Citation | Honda K, et al. (2023) Accumulation of amyloid-beta 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. Neurobiol Aging 123:63-74 |
| abstractText | Apolipoprotein E4 (apoE4) is a risk factor for Alzheimer's disease (AD). Here, we investigated brain amyloid-beta (Abeta) accumulation throughout the aging process in an amyloid precursor protein (APP) knock-in (KI) mouse model of AD that expresses human APP(NL-G-F) with or without human apoE4 or apoE3. Brain Abeta42 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 Abeta42 began in 5-month-old apoE4 mice, and a strong increase in Abeta42 levels was observed in 21-month-old apoE3 mice. Abeta42 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 Abeta42 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 Abeta42 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 Abeta 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. |
