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

Honda, Keiko; Saito, Yuhki; Saito, Haruka; Toyoda, Megumi; Abe, Ruriko; Saito, Takashi; Saido, Takaomi C.; Michikawa, Makoto; Taru, Hidenori; Sobu, Yuriko; Hata, Saori; Nakaya, Tadashi; Suzuki, Toshiharu

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

Honda, Keiko; Saito, Yuhki; Saito, Haruka et al.

Neurobiology of aging, 2023, 123, 63-74

Permalink : https://hdl.handle.net/2115/91973

このアイテムのアクセス数:300件（2026-10-17 00:21 集計）

閲覧可能ファイル

ファイル	フォーマット	サイズ	閲覧回数	説明
Honda et al., 2023 Neurobiol. Aging 123, 63-74	pdf	2.39 MB	342

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

アクセス権	open access
URI	https://hdl.handle.net/2115/91973
タイトル	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
著者	Honda, Keiko ; Saito, Yuhki ; Saito, Haruka ; Toyoda, Megumi ; Abe, Ruriko ; Saito, Takashi ; Saido, Takaomi C. ; Michikawa, Makoto ; Taru, Hidenori ; Sobu, Yuriko ; Hata, Saori ; Nakaya, Tadashi ; Suzuki, Toshiharu
著者名 Honda, Keiko
e-Rad_Researcher 70548180 著者名 Saito, Yuhki
著者名 Saito, Haruka
著者名 Toyoda, Megumi
著者名 Abe, Ruriko
e-Rad_Researcher 40265070 著者名 Saito, Takashi
著者名 Saido, Takaomi C.
著者名 Michikawa, Makoto
e-Rad_Researcher 30533731 著者名 Taru, Hidenori
著者名 Sobu, Yuriko
e-Rad_Researcher 40581012 著者名 Hata, Saori
e-Rad_Researcher 50374559 著者名 Nakaya, Tadashi
e-Rad_Researcher 80179233 著者名 Suzuki, Toshiharu
言語	英語
キーワード	Alzheimer's disease
	Apolipoprotein E
	Gene expression
	Brain aging
	Amyloid-β
発行日	2023-03
出版者	Elsevier
収録物名	Neurobiology of aging
巻(号)	123
ページ	63-74
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 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/
PISSN	0197-4580
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.neurobiolaging.2022.12.003