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Accumulation of amyloid-,B 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
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| Title: | Accumulation of amyloid-,B 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 |
| Authors: | Honda, Keiko Browse this author | | Saito, Yuhki Browse this author →KAKEN DB | | Saito, Haruka Browse this author | | Toyoda, Megumi Browse this author | | Abe, Ruriko Browse this author | | Saito, Takashi Browse this author →KAKEN DB | | Saido, Takaomi C. Browse this author | | Michikawa, Makoto Browse this author | | Taru, Hidenori Browse this author →KAKEN DB | | Sobu, Yuriko Browse this author | | Hata, Saori Browse this author →KAKEN DB | | Nakaya, Tadashi Browse this author →KAKEN DB | | Suzuki, Toshiharu Browse this author →KAKEN DB |
| Keywords: | Alzheimer's disease | | Apolipoprotein E | | Gene expression | | Brain aging | | Amyloid-β |
| Issue Date: | Mar-2023 |
| Publisher: | Elsevier |
| Journal Title: | Neurobiology of aging |
| Volume: | 123 |
| Start Page: | 63 |
| End Page: | 74 |
| Publisher DOI: | 10.1016/j.neurobiolaging.2022.12.003 |
| Abstract: | Apolipoprotein E4 (apoE4) is a risk factor for Alzheimer's disease (AD). Here, we investigated brain amyloid-,B (A,B) 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 A,B42 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 A,B42 began in 5-month-old apoE4 mice, and a strong increase in A,B42 levels was observed in 21-month-old apoE3 mice. A,B42 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 A,B42 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 A,B42 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 A,B 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. |
| Rights: | © 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/91973 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 鈴木 利治
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