ABCA1 and ABCA7: what are their roles in the pathogenesis of Alzheimer's disease?

• Project/Area Number: 25461375
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Nagoya City University
• Principal Investigator: ABE-DOHMAE Sumiko 名古屋市立大学, 大学院医学研究科, 准教授 (70227700)
• Co-Investigator(Kenkyū-buntansha): 道川 誠 名古屋市立大学, 大学院医学研究科, 教授 (40270912)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: ABCA7 / ABCA1 / HDL / アルツハイマー病 / 動脈硬化 / ファゴサイトーシス / コレステロール / apo E / 炎症

Outline of Final Research Achievements

ABCA7 knock-out mice displayed an increased production of endogenous murine amyloid Aβ42 species. Crossing ABCA7-deficient animals to an APP transgenic model resulted in significant increases in the soluble Aβ as compared with mice expressing normal levels of ABCA7. In vitro studies indicated a more rapid endocytosis of APP in ABCA7 knock-out cells that is mechanistically consistent with the increased Aβ production. Phagocytotic activities in peritoneal macrophages were lower even in ABCA7 heterozygous deficiency.

Research Products

• [Int'l Joint Research] Geisel School of Medicine at Dartmouth(米国)
• [Int'l Joint Research] University of Toronto(カナダ)
• [Int'l Joint Research] Chung-Ang University/Hallym University(韓国)
• [Journal Article] Addition of hydrochlorothiazide to angiotensin receptor blocker therapy can achieve a lower sodium balance with no acceleration of intrarenal renin angiotensin system in patients with chronic kidney disease. (2016)
  • Author(s): Fuwa D, Fukuda M, Ogiyama Y, Sato R, Mizuno M, Miura T, Abe-Dohmae S, Michikawa M, Kobori H, Ohte N.
  • Journal Title: J Renin Angiotensin Aldosterone Syst. Volume: 17 Issue: 2
  • DOI: 10.1177/1470320316652032
  • Peer Reviewed / Open Access
• [Journal Article] Phosphatidylcholine protects neurons from toxic effects of amyloid β-protein in culture. (2016)
  • Author(s): Ko M, Hattori T, Abdullah M, Gong JS, Yamane T, Michikawa M.
  • Journal Title: Brain Res. Volume: 1642 Pages: 376-383
  • DOI: 10.1016/j.brainres.2016.04.035
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] ABCG1 and ABCG4 Suppress γ-Secretase Activity and Amyloid β Production (2016)
  • Author(s): Osamu Sano, Maki Tsujita, Yuuji Shimizu, Reiko Kato, Aya Kobayashi, Noriyuki Kioka, Alan T Remaley, Makoto Michikawa, Kazumitsu Ueda, and Michinori Matsuo
  • Journal Title: PLoS One Volume: 11 Issue: 5 Pages: e0155400-e0155400
  • DOI: 10.1371/journal.pone.0155400
  • NAID: 120005997762
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Aβ reduces exosome release from astrocytes by enhancing JNK phosphorylation (2016)
  • Author(s): Abdullah M, Takase H, Nunome M, Enomoto H, Ito J-I, Gong J-S, and Michikawa M.
  • Journal Title: J Alzhiemr Dis, Volume: 53 Issue: 4 Pages: 1433-1441
  • DOI: 10.3233/jad-160292
  • Peer Reviewed
• [Journal Article] Deficiency in the Lipid Exporter ABCA1 Impairs Retrograde Sterol Movement and Disrupts Sterol Sensing at the Endoplasmic Reticulum (2015)
  • Author(s): Yamauchi Y, Iwamoto N, Rogers MA, Abe-Dohmae S, Fujimoto T, Chang CC, Ishigami M, Kishimoto T, Kobayashi T, Ueda K, Furukawa K, Chang TY, Yokoyama S.
  • Journal Title: J Biol Chem Volume: 290 Issue: 39 Pages: 23464-23477
  • DOI: 10.1074/jbc.m115.662668
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] ATP-binding Cassette Transporter A7 (ABCA7) Loss of Function Alters Alzheimer Amyloid Processing (2015)
  • Author(s): Satoh, K. Abe-Dohmae, S. Yokoyama, S. St George-Hyslop, P. Fraser, P. E.
  • Journal Title: J Biol Chem Volume: 290 Issue: 40 Pages: 24152-65
  • DOI: 10.1074/jbc.m115.655076
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Biochemical properties in membrane of rat astrocytes under oxidative stress. (2015)
  • Author(s): Ito J, Nagayasu Y, Ogawa T, Okihara H, Michikawa M.
  • Journal Title: Brain Res. Volume: 1615 Pages: 1-11
  • DOI: 10.1016/j.brainres.2015.04.008
  • Peer Reviewed
• [Journal Article] Arachidonic Acid Diet Attenuates Aβ Deposition in Tg2576 Mice. (2015)
  • Author(s): Hosono T, Nishitsuji K, Nakamura T, Jung CG, Kontani M, Tokuda H, Kawashima H, Kiso Y, Suzuki T, Michikawa M
  • Journal Title: Brain Res Volume: 10 Pages: 1613-1629
  • DOI: 10.1016/j.brainres.2015.04.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Angiotensin type 1a receptor deficiency decreases amyloid β-protein generation and ameliorates brain amyloid pathology. (2015)
  • Author(s): Liu J, Liu S, Matsumoto Y, Murakami S, Sugakawa Y, Kami A, Tanabe C, Maeda T, Michikawa M, Komano H, Zou K.
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 12059-12059
  • DOI: 10.1038/srep12059
  • Peer Reviewed / Open Access
• [Journal Article] Lysophosphatidylcholine increases the neurotoxicity of Alzheimer's amyloid β1-42 peptide: role of oligomer formation. (2015)
  • Author(s): Sheikh AM, Michikawa M, Kim SU, Nagai A.
  • Journal Title: Neuroscience. Volume: 292 Pages: 159-69
  • DOI: 10.1016/j.neuroscience.2015.02.034
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Arachidonic or docosahexaenoic acid diet prevents memory impairment in Tg2576 mice. (2015)
  • Author(s): Hosono T, Mouri A, Nishitsuji K, Jung CG, Kontani M, Tokuda H, Kawashima H, Shibata H, Suzuki T, Nabeshima T, Michikawa M.
  • Journal Title: J Alzheimers Dis Volume: 48 Issue: 1 Pages: 149-162
  • DOI: 10.3233/jad-150341
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Auraptene increases the production of amyloid-beta via c-Jun N-terminal kinase-dependent activation of γ-secretase. (2015)
  • Author(s): Jung CG, Uhm KO, Horike H, Kim MJ, Misumi S, Ishida A, Ued Y, Choi EK, Kim YS, Michikawa M, Hida H.
  • Journal Title: J Alzheimers Dis Volume: 43 Issue: 4 Pages: 1215-1228
  • DOI: 10.3233/jad-141692
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ATBF1 is a novel amyloid-β protein precursor protein (AβPP) binding protein that affects APP expression (2015)
  • Author(s): Uhm KO, Kim MJ, Kawaguchi M, Akatsu H, Miura Y, Misumi S, Hida H, Choi EK, Kim YS, Michikawa M, Jung CG.
  • Journal Title: J Alzheimers Dis Volume: 43 Issue: 1 Pages: 243-257
  • DOI: 10.3233/jad-140612
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Preferential Incorporation of Shorter and Less Unsaturated Acyl Phospholipids into High Density Lipoprotein-Like Particles in the ABCA1- and ABCA7-mediated Biogenesis with apoA-I (2015)
  • Author(s): Noriko Hotta, Sumiko Abe-Dohmae, Ryo Taguchi, and Shinji Yokoyama
  • Journal Title: Chemistry and Physics of Lipids Volume: 187 Pages: 1-9
  • DOI: 10.1016/j.chemphyslip.2015.01.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Astrocytes endogenous apoE generates HDL-like lipoproteins using previously synthesized cholesterol through interaction with ABCA1 (2014)
  • Author(s): Ito, J. Nagayasu, Y. Miura, Y. Yokoyama, S. Michikawa, M.
  • Journal Title: Brain Res Volume: 1570 Pages: 1-12
  • DOI: 10.1016/j.brainres.2014.04.037
  • Peer Reviewed
• [Journal Article] Involvement of cdc42/Rho kinase in apoA-I-mediated cholesterol efflux through interaction between cytosolic lipid-protein particles and microtubules in rat astrocytes. (2014)
  • Author(s): 11. Kheirollah A., Nagayasu Y., Ueda H., Yokoyama S. Michikawa M. and Ito J.
  • Journal Title: J. Neurosci. Res. Volume: 92 Issue: 4 Pages: 455-463
  • DOI: 10.1002/jnr.23324
  • Peer Reviewed
• [Journal Article] Liquid diet induces memory impairment accompanied by a decreased number of hippocampal neurons in mice. (2014)
  • Author(s): Okihara H, Ito J, Kokai S, Ishida T, Hiranuma M, Kato C, Yabushita T, Ishida K, Ono T, Michikawa M.
  • Journal Title: J Neurosci Res. Volume: 92 Issue: 8 Pages: 1010-7
  • DOI: 10.1002/jnr.23383
  • Peer Reviewed
• [Journal Article] Increasing Cellular Level of Phosphatidic Acid Enhances FGF-1 Production in Long Term-cultured Rat Astrocytes (2014)
  • Author(s): Yuko Nagayasu, Shin-ya Morita, Hideki Hayashi, Yutaka Miura, Kazuki Yokoyama, Makoto Michikawa, Jin-ichi Ito
  • Journal Title: Brain Research Volume: 1563 Pages: 31-40
  • DOI: 10.1016/j.brainres.2014.03.035
  • Peer Reviewed
• [Journal Article] KSGal6ST is essential for the 6-sulfation of galactose within keratan sulfate in early postnatal brain. (2014)
  • Author(s): Hoshino H, Foyez T, Ohtake-Niimi S, Takeda-Uchimura Y, Michikawa M, Kadomatsu K, Uchimura K.
  • Journal Title: J Histochem Cytochem. Volume: 62 Issue: 2 Pages: 145-156
  • DOI: 10.1369/0022155413511619
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Enhancement of FGF-1 release along with cytosolic proteins from rat astrocytes by hydrogen peroxide. (2013)
  • Author(s): Ito J, Nagayasu Y, Hoshikawa M, Kato KH, Miura Y, Asai K, Hayashi H, Yokoyama S, Michikawa M.
  • Journal Title: Brain Res. Volume: 1522 Pages: 12-21
  • DOI: 10.1016/j.brainres.2013.05.035
  • Peer Reviewed
• [Journal Article] Tooth loss induces memory impairment and neuronal cell loss in APP transgenic mice. (2013)
  • Author(s): Oue H, Miyamoto Y, Okada S, Koretake K, Jung CG, Michikawa M, Akagawa Y.
  • Journal Title: Behav Brain Res. Volume: 252(1) Pages: 318-325
  • DOI: 10.1016/j.bbr.2013.06.015
  • Peer Reviewed
• [Journal Article] Aβ43 is the earliest depositing Aβ species in APP transgenic mouse brain and is converted to Aβ41 by two active domains of ACE. (2013)
  • Author(s): Zou K, Liu J, Watanabe A, Hiraga S, Liu S, Tanabe C, Maeda T, Terayama Y, Takahashi S, Michikawa M, Komano H
  • Journal Title: Am J Pathol Volume: 182 Issue: 6 Pages: 2311-2331
  • DOI: 10.1016/j.ajpath.2013.01.053
  • Peer Reviewed
• [Presentation] 脂質代謝異常による骨髄由来肥満細胞の分化と機能への影響についての検討 (2017)
  • Author(s): 浅井遥, 深見優衣, 堂前純子, 福石信之
  • Organizer: 日本薬学会（宮城県仙台市）
  • Place of Presentation: 仙台国際センター
• [Presentation] グリア細胞における ABCA7 発現制御機構の検討 (2016)
  • Author(s): 市野晨人, 奥平桂一郎, 川原遥華, 木村仁, 辻大輔, 西辻和親, 堂 純子, 道川誠, 坂下直実, 伊藤孝司, 斎藤博幸
  • Organizer: 日本薬学会
  • Place of Presentation: 横浜 パシフィコ横浜
  • Year and Date: 2016-03-29
• [Presentation] ABCA7遺伝子型とファゴサイトーシス活性 (2016)
  • Author(s): 堂前純子, 高瀬弘嗣, 吉武仙達, 道川誠
  • Organizer: 日本動脈硬化学会（東京都新宿区）
  • Place of Presentation: 京王プラザホテル
• [Presentation] Serum amyloid Aの代謝回転とABCA1 (2014)
  • Author(s): 堂前純子, 磯野裕司, 横山信治, 道川誠
  • Organizer: 日本生化学会
  • Place of Presentation: 京都 国立京都国際会館
  • Year and Date: 2014-10-18
• [Presentation] SAA turnover is modulated by ABCA1 (2014)
  • Author(s): Sumiko Abe-Dohmae, Yuji Isono, Shinji Yokoyama, Makoto Michikawa
  • Organizer: 日本動脈硬化学会
  • Place of Presentation: 東京 京王プラザホテル
  • Year and Date: 2014-07-11
• [Presentation] SAA turnover is modulated by ABCA1 (2014)
  • Author(s): Sumiko Abe-Dohmae, Yuji Isono, Shinji Yokoyama, Makoto Michikawa
  • Organizer: 第46回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 京王プラザホテル (新宿）