iPS細胞技術を用いたアルツハイマー病の遺伝子解析と付加的考察

//背景//---
人の細胞を初期化遺伝子によってiPS細胞にした時の
遺伝子的なダイナミクスがどのようであるか？
これに関しては未知の部分もあるのではないかと拝察します。
しかし、医学生理学の研究を行う上で
iPS細胞が持つ1つの重要な価値は
「もともとあった遺伝情報の(一部?)が残る」
ということです。
従って、パーキンソン病の人から脳以外の細胞を取得して
iPS細胞にして、そこから脳の細胞に分化させたときには
そのパーキンソン病の遺伝的な特質が反映されるということです。
皮膚や血液のように簡単に採取できる細胞に対して
脳や臓器の細胞は簡単に採取できないので、
簡単に採取できない細胞について調べるときには
iPS細胞が有用であるということです。
特に血液などは保存することができるし、
多くのサンプルを残すことができるので、
実際の人、患者さんの細胞でメタ分析をすることができます。
---
Takayuki Kondo(敬称略)ら大規模な医療研究グループは
アルツハイマー病の患者さん102名から作製した
iPS細胞を大脳皮質のニューロンに分化させて、
そのニューロンの遺伝子解析を行われています(1)。
その内容の一部と筆者の視点、調査、考察を合わせて
読者の方と情報共有したいと思います。
(関連グループ)
Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI)

//結果(1)//---
アルツハイマー病の因子と考えられる
アミロイドβの産生に関わる24(染色体内)遺伝子を特定。
最もP値が低く関連性が高かったのは
染色体11番のDENND2B。
(参考文献(1) Table.1より)
その24遺伝子のうち
CUL1, QRFP, CTNNA3, DAB1 and DCC
これらはアミロイドβの産生に関わると知られています(8-13)。
そのうち
MAGI1,  TMTC1,  TRPM1,  KCNMA1,  DAB1, 
CPXM2, ROBO2 and ANO3
これらはアルツハイマー病の患者さん(臨床結果)
と関わりのある遺伝子です(14-21)。
-
12の遺伝子については新たに発見されました。
(参考文献(1) Supplementary Table 3 (NA)より)
-
抽出された遺伝子に関わる代謝機能は
Calcium signaling pathwayの異常が大きいです。
 (Extended Data Fig. 5d)
これはアルツハイマー病の代謝機能と関連があります(22)。
---
遺伝子ノックダウンから最も影響を与えた遺伝子とその機能。
↓
<Aβ42/40比(悪性/良性)>
CTNNA3, ANO3 and CSMD1.
・CTNNA3
細胞と細胞の接着機能を持つ。
・ANO3
細胞内のカルシウム信号。
・CSMD1
自分の細胞を見分ける補完システムを持つ。
-
<タンパク質量を減らした遺伝子>
QRFPR,  INFLR1,  ZNRF2,  ROBO2,  DCC  and  APP  
・QRFPR
アミロイドβ毒性から神経細胞を守る。
・INFLR1、ZNRF2
機能不明。
・ROBO2
脳脊髄液のアミロイドβを減らした。
・DCC
アミロイドβタンパク質を制御する。
---
iPS細胞から分化させた患者さん由来の神経細胞の
遺伝子的特徴を組み込んで計算すると
そうではない場合と比べて、
画像データとの相関性が高まったとされています。
これはアミロイドβの場合。
一方、タウタンパク質では見られませんでした。
---

//疑問//---
脳の細胞種といえば、神経細胞、乏突起膠細胞、マイクログリア、
星状膠細胞などがありますが、
その中でも細胞種を決める遺伝子的な特徴は
一点に収束するのではなく
Francisco J. Garcia, Na Sun(敬称略)らが
Fig.1bで示すようにある範囲をもっています(2)。
転写、翻訳後、細胞が発出しているタンパク質が異なる
ということです。
Francisco J. Garcia氏らは脳の血管の細胞種を
細かく分類されています(2)。
そうしたときにiPS細胞で分化させた神経細胞の
遺伝子的なばらつきは実際の脳の神経細胞の
遺伝子的なばらつきとどのように異なるか？
ということです。
例えば、iPS細胞で人工的に作り出した神経細胞群の
遺伝子的な特徴の一致度は体内にある神経細胞群よりも
顕著に高く、より収束しているのか？
ということです。
---
これは重要な意味を持ちます。
例えば、
①患者さんのアルツハイマー病変のある神経細胞。
②その患者さんの血液細胞からiPSC技術を用いて
　人工的に生み出した神経細胞。
これら①、②の表面タンパク質が一致しているか？
これは少しこの記事の趣旨とは異なるのですが、
iPS細胞技術を用いて、
細胞種特異的輸送系統(Cell-type-specific delivery system）
における特異的標的を見つけることができるかどうか？
ということに関わります。

//考察//---
Takayuki Kondo氏らは今回は(Ref.(1))大脳皮質の神経細胞に
焦点を当てて、その中で詳しい遺伝子解析をしましたが、
グリア細胞、転写因子なども含めて
もっと高次に分析していく必要性があると言及されています(1)。
おそらくアミロイドβやタウタンパク質などの
アルツハイマー病の原因となるたんぱく質の蓄積は
単に細胞(小胞体など)から生み出されるわけではなく、
オートファジーなどによるタンパク質の分解や
間質液の循環によるタンパク質の排出、
あるいは血管からの細胞やサイトカインの流入など
様々な要因が関わっていると考えられます。
Andrew C. Yang(敬称略)ら医療研究グループは
脳の血液、血管に着目した遺伝子解析を
アルツハイマーのリスクに対して行われています(3)。
その結果、30のリスク遺伝子が見つかったとされています(3)。
--
Takayuki Kondo氏らの日本を中心とした遺伝子解析は
(iPS細胞を使った)プロトコルとしても、
一要素(今回は神経細胞)としても
非常に重要な意義を持ちます(1)。
それを通じて、実際に患者さんに治療をするときには、
・脳の様々な部位
・神経細胞(1)、グリア細胞、血液組織(その細胞群(2,3))
・核遺伝子(DNA)、転写遺伝子(mRNA)
・組織学(画像診断)、血液バイオマーカー
・実質的な機能評価(身体機能、認知機能など)
これらの解析を包括的に行い
全体的として治療を行っていく必要があるのではないか？
このように考えました。

//考察//---
Takayuki Kondo氏らは今回は(Ref.(1))大脳皮質の神経細胞に
焦点を当てて、その中で詳しい遺伝子解析をしましたが、
グリア細胞(細胞種特異性:Cell-type specificity)
転写因子なども含めて
もっと高次に分析していく必要性があると言及されています(1)。
---
神経細胞に対するグリア細胞の比率は高等生物になるほど
高くなると言われています。
線虫 6:1(神経細胞:グリア細胞)
マウス 3:1(神経細胞:グリア細胞)
人 1.4:1(神経細胞:グリア細胞)
このようにいわれています。
特に、グリア細胞の中で星状膠細胞が多いと言われています。
以前はアミロイドβは主に神経細胞から産生されると
言われていましたが、星状膠細胞は産生や蓄積量において
重要な役割を果たしていると言われています(4)。
人においては、グリア細胞が多いので、
マウスのケースと比べて、星状膠細胞などの
アルツハイマー病に対する影響は大きい可能性があります。

//意見//---
Takayuki Kondo氏らの研究で、タウタンパク質に関しては
細胞の遺伝子的特徴と画像診断による結果との相関が
低いことが明らかになりました(1)。
「相関が低い」というデータもそれが高いという事と
同様に大きな医学生理学的な意味を持つと考えます。
なぜなら、相対的な評価で
アミロイドβよりもタウタンパク質は
神経細胞よりも(おそらく)グリア細胞による作用が
大きいかもしれないという事がわかるからです。
また、従来のマイクログリアと星状膠細胞が
タウの病理に関係するという報告と紐づけることができます(5-7)。
--
従って、一つ一つ切り分けて丁寧に評価する事で
どういった細胞が遺伝子的に
アミロイドβやタウタンパク質と
どの程度関与しているかというのがわかる可能性があります。

//まとめ//---
医療はビックデータを扱う時代に入ったと言われています。
今回の遺伝子解析もマルチオミックス解析の一つで
ビックデータによる解析になります。
しかし、そのビックデータをどのようにつなげて
あるいはどういうビックデータをとるか？
その前提の条件をどう定めるか？
それらをどう創薬、臨床に生かすか？
このような事は人による
医学生理学の詳しい理解が必要になります。
今回のアルツハイマー病のデータも
神経細胞の遺伝子解析を人のケースで実施されています。
Takayuki Kondo氏らが
今回の取り組みを「2次元的」と評されています(1)。
2次元からより高次に展開していくときに
同じようにコンピューターの力は必要ですが、
それをどのように設定するかは非常に重要です。
詳細と全体、スケールの可動性などを組み込んだ
包括的な理解が必要になります。

(参考文献)
(1)
Takayuki Kondo, Norikazu Hara, Satoshi Koyama, Yuichiro Yada, Kayoko Tsukita, Ayako Nagahashi, Takeshi Ikeuchi, Kenji Ishii, Takashi Asada, Tetsuaki Arai, Ryo Yamada, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, John Morris, Leslie M. Shaw, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, John C. Morris, Maria Carroll, Mary L. Creech, Erin Franklin, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, Randall Griffith, David Clark, David Geldmacher, John Brockington, Erik Roberson, Marissa Natelson Love, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Daniel Varon, Maria T. Greig, Peggy Roberts, Marilyn Albert, Chiadi Onyike, Daniel D’Agostino, Stephanie Kielb, James E. Galvin, Brittany Cerbone, Christina A. Michel, Dana M. Pogorelec, Henry Rusinek, Mony J. de Leon, Lidia Glodzik, Susan De Santi, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Ruth A. Mulnard, Gaby Thai, Catherine Mc-Adams-Ortiz, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H. S. Silverman, Po H. Lu, George Bartzokis, Neill R. Graff-Radford, Francine Parfitt, Tracy Kendall, Heather Johnson, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Cynthia Hunt, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Howard Feldman, Benita Mudge, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek Marsel Mesulam, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T.-Y. Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Steven G. Potkin, Adrian Preda, Dana Nguyen, Pierre Tariot, Anna Burke, Nadira Trncic, Adam Fleisher, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Anahita Adeli, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Leslie Gordineer, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Henry Querfurth, Geoffrey Tremont, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Norman Relkin, Gloria Chaing, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj & Kristin Fargher Takeshi Iwatsubo, Takashi Asada, Hiroyuki Arai, Morihiro Sugishita, Hiroshi Matsuda, Kengo Ito, Michio Senda, Kenji Ishii, Ryozo Kuwano, Takeshi Ikeuchi, Noriko Sato, Hajime Sato, Shun Shimohama, Masaki Saitoh, Rika Yamauchi, Takashi Hayashi, Seiju Kobayashi, Norihito Nakano, Junichiro Kanazawa, Takeshi Ando, Chiyoko Takanami, Masato Hareyama, Masamitsu Hatakenaka, Eriko Tsukamoto, Shinji Ochi, Mikio Shoji, Etsuro Matsubara, Takeshi Kawarabayashi, Yasuhito Wakasaya, Takashi Nakata, Naoko Nakahata, Shuichi Ono, Yoshihiro Takai, Satoshi Takahashi, Hisashi Yonezawa, Junko Takahashi, Masako Kudoh, Makoto Sasaki, Yutaka Matsumura, Yohsuke Hirata, Tsuyoshi Metoki, Susumu Hayakawa, Yuichi Sato, Masayuki Takeda, Toshiaki Sasaki, Koichiro Sera, Kazunori Terasaki, Yoshihiro Saitoh, Shoko Goto, Kuniko Ueno, Hiromi Sakashita, Kuniko Watanabe, Ken Nagata, Yuichi Sato, Tetsuya Maeda, Yasushi Kondoh, Takashi Yamazaki, Daiki Takano, Mio Miyata, Hiromi Komatsu, Mayumi Watanabe, Tomomi Sinoda, Rena Muraoka, Kayoko Kikuchi, Hitomi Ito, Aki Sato, Toshibumi Kinoshita, Hideyo Toyoshima, Kaoru Sato, Shigeki Sugawara, Isao Ito, Fumiko Kumagai, Hiroyuki Arai, Katsutoshi Furukawa, Masaaki Waragai, Naoki Tomita, Nobuyuki Okamura, Mari Ootsuki, Katsumi Sugawara, Satomi Sugawara, Shunji Mugikura, Atsushi Umetsu, Takanori Murata, Tatsuo Nagasaka, Yukitsuka Kudo, Manabu Tashiro, Shoichi Watanuki, Masatoyo Nishizawa, Takeshi Ikeuchi, Takayoshi Tokutake, Saeri Ishikawa, Emiko Kishida, Nozomi Sato, Mieko Hagiwara, Kumi Yamanaka, Takeyuki Watanabe, Taeko Takasugi, Shoichi Inagawa, Kenichi Naito, Masanori Awaji, Tsutomu Kanazawa, Kouiti Okamoto, Masaki Ikeda, Tsuneo Yamazaki, Yuiti Tasiro, Syunn Nagamine, Shiori Katsuyama, Sathiko Kurose, Sayuri Fukushima, Etsuko Koya, Makoto Amanuma, Noboru Oriuti, Kouiti Ujita, Kazuhiro Kishi, Kazuhisa Tuda, Takashi Asada, Katsuyoshi Mizukami, Tetsuaki Arai, Etsuko Nakajima, Katsumi Miyamoto, Kousaku Saotome, Tomoya Kobayashi, Saori Itoya, Jun Ookubo, Toshiya Akatsu, Yoshiko Anzai, Junya Ikegaki, Yuuichi Katou, Kaori Kimura, Ryou Kuchii, Hajime Saitou, Kazuya Shinoda, Satoka Someya, Hiroko Taguchi, Kazuya Tashiro, Masaya Tanaka, Tatsuya Nemoto, Ryou Wakabayashi, Daisuke Watanabe, Harumasa Takano, Tetsuya Suhara, Hitoshi Shinoto, Hitoshi Shimada, Makoto Higuchi, Takaaki Mori, Hiroshi Ito, Takayuki Obata, Yoshiko Fukushima, Kazuko Suzuki, Izumi Izumida, Katsuyuki Tanimoto, Takahiro Shiraishi, Hitoshi Shinotoh, Hitoshi Shimada, Junko Shiba, Hiroaki Yano, Miki Satake, Aimi Nakui, Yae Ebihara, Tomomi Hasegawa, Yasumasa Yoshiyama, Mami Kato, Yuki Ogata, Hiroyuki Fujikawa, Nobuo Araki, Yoshihiko Nakazato, Takahiro Sasaki, Tomokazu Shimadu, Kimiko Yoshimaru, Hiroshi Matsuda, Etsuko Imabayashi, Asako Yasuda, Etuko Yamamoto, 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Toriihara, Shinichi Ohtani, Toshifumi Matsui, Yu Hayasaka, Tomomi Toyama, Hideki Sakurai, Kumiko Sugiura, Hirofumi Taguchi, Shizuo Hatashita, Akari Imuta, Akiko Matsudo, Daichi Wakebe, Hideki Hayakawa, Mitsuhiro Ono, Takayoshi Ohara, Yukihiko Washimi, Yutaka Arahata, Akinori Takeda, Yoko Konagaya, Akiko Yamaoka, Masashi Tsujimoto, Hideyuki Hattori, Takashi Sakurai, Miura Hisayuki, Hidetoshi Endou, Syousuke Satake, Young Jae Hong, Katsunari Iwai, Kenji Yoshiyama, Masaki Suenaga, Sumiko Morita, Teruhiko Kachi, Kenji Toba, Rina Miura, Takiko Kawai, Ai Honda, Kengo Itou, Takashi Kato, Ken Fujiwara, Rikio Katou, Mariko Koyama, Naohiko Fukaya, Akira Tsuji, Hitomi Shimizu, Hiroyuki Fujisawa, Tomoko Nakazawa, Satoshi Koyama, Takanori Sakata, Masahito Yamada, Mitsuhiro Yoshita, Miharu Samuraki, Kenjiro Ono, Moeko Shinohara, Yuki Soshi, Kozue Niwa, Chiaki Doumoto, Mariko Hata, Miyuki Matsushita, Mai Tsukiyama, Nozomi Takeda, Sachiko Yonezawa, Ichiro Matsunari, Osamu Matsui, Fumiaki Ueda, Yasuji Ryu, Masanobu Sakamoto, Yasuomi Ouchi, Yasuomi Ouchi, Madoka Chita, Yumiko Fujita, Rika Majima, Hiromi Tsubota, Umeo Shirasawa, Masashi Sugimori, Wataru Ariya, Yuuzou Hagiwara, Yasuo Tanizaki, Hidenao Fukuyama, Ryosuke Takahashi, Hajime Takechi, Chihiro Namiki, Kengo Uemura, Takeshi Kihara, Hiroshi Yamauchi, Shizuko Tanaka-Urayama, Emiko Maeda, Natsu Saito, Shiho Satomi, Konomi Kabata, Shin-Ichi Urayama, Tomohisa Okada, Koichi Ishizu, Shigeto Kawase, Satoshi Fukumoto, Masanori Nakagawa, Takahiko Tokuda, Masaki Kondo, Fumitoshi Niwa, Toshiki Mizuno, Yoko Oishi, Mariko Yamazaki, Daisuke Yamaguchi, Kyoko Ito, Yoku Asano, Chizuru Hamaguchi, Kei Yamada, Chio Okuyama, Kentaro Akazawa, Shigenori Matsushima, Takamasa Matsuo, Toshiaki Nakagawa, Takeshi Nii, Takuji Nishida, Kuniaki Kiuchi, Masami Fukusumi, Hideyuki Watanabe, Toshiaki Taoka, Akihiro Nogi, Masatoshi Takeda, Toshihisa Tanaka, Naoyuki Sato, Hiroaki Kazui, Kenji Yoshiyama, Takashi Kudo, Masayasu Okochi, Takashi Morihara, Shinji Tagami, Noriyuki Hayashi, Masahiko Takaya, Tamiki Wada, Mikiko Yokokoji, Hiromichi Sugiyama, Daisuke Yamamoto, Shuko Takeda, Keiko Nomura, Mutsumi Tomioka, Eiichi Uchida, Yoshiyuki Ikeda, Mineto Murakami, Takami Miki, Hiroyuki Shimada, Suzuka Ataka, Motokatsu Kanemoto, Jun Takeuchi, Akitoshi Takeda, Rie Azuma, Yuki Iwamoto, Naomi Tagawa, Junko Masao, Yuka Matsumoto, Yuko Kikukawa, Hisako Fujii, Junko Matsumura, Susumu Shiomi, Joji Kawabe, Yoshihiro Shimonishi, Yukio Miki, Mitsuji Higashida, Tomohiro Sahara, Takashi Yamanaga, Shinichi Sakamoto, Hiroyuki Tsushima, Kiyoshi Maeda, Yasuji Yamamoto, Toshio Kawamata, Kazuo Sakai, Haruhiko Oda, Takashi Sakurai, Taichi Akisaki, Mizuho Adachi, Masako Kuranaga, Sachi Takegawa, Yoshihiko Tahara, Seishi Terada, Takeshi Ishihara, Hajime Honda, Osamu Yokota, Yuki Kishimoto, Naoya Takeda, Nao Imai, Mayumi Yabe, Kentaro Ida, Daigo Anami, Seiji Inoue, Toshi Matsushita, Reiko Wada, Shinsuke Hiramatsu, Hiromi Tonbara, Reiko Yamamoto, Kenji Nakashima, 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Megumi Shimamura, Mikiko Sugiyama, Atsushi Watanabe, Naomi Oota, Shigeo Takebayashi, Yoshigazu Hayakawa, Mitsuhiro Idegawa, Noriko Toya & Kazunari Ishii & Haruhisa Inoue 
Dissection of the polygenic architecture of neuronal Aβ production using a large sample of individual iPSC lines derived from Alzheimer’s disease patients
Nature Aging volume 2, pages125–139 (2022)
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Author information
Affiliations
Medical-risk Avoidance based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Kyoto, Japan
Takayuki Kondo, Ayako Nagahashi & Haruhisa Inoue
Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
Takayuki Kondo, Yuichiro Yada, Kayoko Tsukita, Ayako Nagahashi & Haruhisa Inoue
iPSC-based Drug Discovery and Development Team, RIKEN BioResource Research Center (BRC), Kyoto, Japan
Takayuki Kondo, Yuichiro Yada, Kayoko Tsukita & Haruhisa Inoue
Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan
Norikazu Hara & Takeshi Ikeuchi
Unit of Statistical Genetics, Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Satoshi Koyama & Ryo Yamada
Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
Kenji Ishii
Department of Psychiatry, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
Takashi Asada & Tetsuaki Arai
Institute for Advancement of Clinical and Translational Science (iACT), Kyoto University Hospital, Kyoto, Japan
Haruhisa Inoue
Magnetic Resonance Unit at the VA Medical Center and Radiology, Medicine, Psychiatry and Neurology, University of California, San Francisco, CA, USA
Michael W. Weiner, Sara S. Mason, Colleen S. Albers, David Knopman & Kris Johnson
UC San Diego School of Medicine, University of California, La Jolla, CA, USA
Paul Aisen
Neurology, Mayo Clinic, Rochester, MN, USA
Ronald Petersen
Radiology, Mayo Clinic, Rochester, MN, USA
Clifford R. Jack
University of California, Berkeley, Berkeley, CA, USA
William Jagust
University of Pennsylvania, Philadelphia, PA, USA
John Q. Trojanowki
University of Southern California, Los Angeles, CA, USA
Arthur W. Toga, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro & Bryan M. Spann
University of California, Davis, Davis, CA, USA
Laurel Beckett
Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Robert C. Green
Washington University, St. Louis, MO, USA
John Morris, Leslie M. Shaw, Beau Ances, John C. Morris, Maria Carroll, Mary L. Creech, Erin Franklin, Mark A. Mintun, Stacy Schneider & Angela Oliver
Oregon Health and Science University, Portland, OR, USA
Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter & Sara Dolen
University of California, San Diego, San Diego, CA, USA
James Brewer, Helen Vanderswag & Adam Fleisher
University of Michigan, Ann Arbor, MI, USA
Judith L. Heidebrink & Joanne L. Lord
Baylor College of Medicine, Houston, TX, USA
Rachelle S. Doody, Javier Villanueva-Meyer, Munir Chowdhury, Susan Rountree & Mimi Dang
Columbia University Medical Center, New York, NY, USA
Yaakov Stern, Lawrence S. Honig & Karen L. Bell
University of Alabama, Birmingham, AL, USA
Daniel Marson, Randall Griffith, David Clark, David Geldmacher, John Brockington, Erik Roberson & Marissa Natelson Love
Mount Sinai School of Medicine, New York, NY, USA
Hillel Grossman & Effie Mitsis
Rush University Medical Center, Chicago, IL, USA
Raj C. Shah & Leyla deToledo-Morrell
Wien Center, Miami Beach, FL, USA
Ranjan Duara, Daniel Varon, Maria T. Greig & Peggy Roberts
Johns Hopkins University, Baltimore, MD, USA
Marilyn Albert, Chiadi Onyike, Daniel D’Agostino & Stephanie Kielb
New York University, New York, NY, USA
James E. Galvin, Brittany Cerbone, Christina A. Michel, Dana M. Pogorelec, Henry Rusinek, Mony J. de Leon, Lidia Glodzik & Susan De Santi
Duke University Medical Center, Durham, NC, USA
P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong & Edward Coleman
University of Kentucky, Lexington, KY, USA
Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates & Gary Conrad
University of Rochester Medical Center, Rochester, NY, USA
Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail & Connie Brand
University of California, Irvine, Irvine, CA, USA
Ruth A. Mulnard, Gaby Thai & Catherine Mc-Adams-Ortiz
University of Texas Southwestern Medical School, Dallas, TX, USA
Kyle Womack, Dana Mathews & Mary Quiceno
Emory University, Atlanta, GA, USA
Allan I. Levey, James J. Lah & Janet S. Cellar
University of Kansas Medical Center, Kansas City, KS, USA
Jeffrey M. Burns, Russell H. Swerdlow & William M. Brooks
Indiana University, Bloomington, IN, USA
Liana Apostolova, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring & Cynthia Hunt
Universityof California, Los Angeles, Los Angeles, CA, USA
Kathleen Tingus, Ellen Woo, Daniel H. S. Silverman, Po H. Lu & George Bartzokis
Mayo Clinic, Jacksonville, FL, USA
Neill R. Graff-Radford, Francine Parfitt, Tracy Kendall & Heather Johnson
Yale University School of Medicine, New Haven, CT, USA
Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy & Pradeep Varma
McGill University and Jewish General Hospital, Montreal, Quebec, Canada
Howard Chertkow, Howard Bergman & Chris Hosein
Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
Sandra Black, Bojana Stefanovic & Curtis Caldwell
UBC Clinic for Alzheimer Disease and Related Disorders, Vancouver, British Columbia, Canada
Ging-Yuek Robin Hsiung, Howard Feldman, Benita Mudge & Michele Assaly
Cognitive Neurology–St. Joseph’s, London, Ontario, Canada
Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost & Andrew Kertesz
Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA
Charles Bernick & Donna Munic
Northwestern University, Evanston, IL, USA
Marek Marsel Mesulam, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu & Nancy Johnson
Premiere Research Institute and Palm Beach Neurology, West Palm Beach, FL, USA
Carl Sadowsky & Teresa Villena
Georgetown University Medical Center, Washington, DC, USA
Raymond Scott Turner, Kathleen Johnson & Brigid Reynolds
Brigham and Women’s Hospital, Boston, MA, USA
Reisa A. Sperling, Keith A. Johnson & Gad Marshall
Stanford University, Stanford, CA, USA
Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen & Jared Tinklenberg
Banner Sun Health Research Institute, Sun City, AZ, USA
Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson & Sherye A. Sirrel
Boston University, Boston, MA, USA
Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash & Patricia Lynn Johnson
Howard University, Boston, DC, USA
Thomas O. Obisesan, Saba Wolday & Joanne Allard
Case Western Reserve University, Cleveland, OH, USA
Alan Lerner, Paula Ogrocki, Curtis Tatsuoka & Parianne Fatica
UC Davis School of Medicine, Sacramento, CA, USA
Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli & Owen Carmichael
Neurological Care of CNY, Syracuse, NY, USA
Smita Kittur
Parkwood Hospital, Philadelphia, PA, USA
Michael Borrie, T.-Y. Lee & Rob Bartha
University of Wisconsin, Madison, WI, USA
Sterling Johnson, Sanjay Asthana & Cynthia M. Carlsson
University of California, Irvine, Irvine, CA, USA
Steven G. Potkin, Adrian Preda & Dana Nguyen
Banner Alzheimer’s Institute, Phoenix, AZ, USA
Pierre Tariot, Anna Burke, Nadira Trncic, Adam Fleisher & Stephanie Reeder
DENT Neurologic Institute, New York, NY, USA
Vernice Bates, Horacio Capote & Michelle Rainka
Ohio State University, Columbus, OH, USA
Douglas W. Scharre, Maria Kataki & Anahita Adeli
Albany Medical College, Albany, NY, USA
Earl A. Zimmerman, Dzintra Celmins & Alice D. Brown
Hartford Hospital, Olin Neuropsychiatry Research Center, Hartford, CT, USA
Godfrey D. Pearlson, Karen Blank & Karen Anderson
Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
Laura A. Flashman, Marc Seltzer, Mary L. Hynes & Robert B. Santulli
Wake Forest University Health Sciences, Winston-Salem, NC, USA
Kaycee M. Sink, Leslie Gordineer, Jeff D. Williamson, Pradeep Garg & Franklin Watkins
Rhode Island Hospital, Providence, RI, USA
Brian R. Ott, Henry Querfurth & Geoffrey Tremont
Butler Hospital, Providence, RI, USA
Stephen Salloway, Paul Malloy & Stephen Correia
University of California, San Francisco, San Francisco, CA, USA
Howard J. Rosen, Bruce L. Miller & David Perry
Medical University of South Carolina, Charleston, SC, USA
Jacobo Mintzer, Kenneth Spicer & David Bachman
Nathan Kline Institute, Orangeburg, NY, USA
Nunzio Pomara, Raymundo Hernando & Antero Sarrael
Cornell University, Ithaca, NY, USA
Norman Relkin, Gloria Chaing, Michael Lin & Lisa Ravdin
USF Health Byrd Alzheimer’s Institute, University of South Florida, Tampa, FL, USA
Amanda Smith, Balebail Ashok Raj & Kristin Fargher
University of Tokyo, Tokyo, Japan
Takeshi Iwatsubo
Tsukuba University, Tsukuba, Japan
Takashi Asada
Tohoku University, Sendai, Japan
Hiroyuki Arai
Institute of Brain and Blood Vessels, Isesaki, Japan
Morihiro Sugishita
National Center of Neurology and Psychiatry, Kodaira, Japan
Hiroshi Matsuda, Noriko Sato & Hajime Sato
National Center of Geriatrics and Gerontology, Tokyo, Japan
Kengo Ito, Teruhiko Kachi & Kenji Toba
Institute of Biomedical Research and Innovation, Kobe, Japan
Michio Senda
Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan
Kenji Ishii
Niigata University, Niigata, Japan
Ryozo Kuwano & Takeshi Ikeuchi
Department of Neurology, Sapporo Medical University, Sapporo, Japan
Shun Shimohama, Masaki Saitoh, Rika Yamauchi, Takashi Hayashi & Chiyoko Takanami
Department of Neuropsychiatry, Sapporo Medical University, Sapporo, Japan
Seiju Kobayashi
Department of Clinical Psychology, School of Psychological Science, Health Sciences University of Hokkaido, Sapporo, Japan
Norihito Nakano
School of Psychological Science, Health Sciences University of Hokkaido, Sapporo, Japan
Junichiro Kanazawa
Graduate School of Psychological Science, Health Sciences University of Hokkaido, Sapporo, Japan
Takeshi Ando
Department of Radiology, Sapporo Medical University, Sapporo, Japan
Masato Hareyama
Division of Diagnostic Radiology, Sapporo Medical University, Sapporo, Japan
Masamitsu Hatakenaka
Social Medical Corporation Teishinkai Central CI Clinic, Sapporo, Japan
Eriko Tsukamoto
Radiology Department, Social Medical Corporation Teishinkai Central CI Clinic, Sapporo, Japan
Shinji Ochi
Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
Mikio Shoji, Etsuro Matsubara, Takeshi Kawarabayashi, Yasuhito Wakasaya, Takashi Nakata & Naoko Nakahata
Department of Radiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
Shuichi Ono & Yoshihiro Takai
Division of Neurology and Gerontology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
Satoshi Takahashi, Hisashi Yonezawa, Junko Takahashi, Masako Kudoh, Kuniko Ueno, Hiromi Sakashita & Kuniko Watanabe
Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Morioka, Japan
Makoto Sasaki
Center for Radiological Sciences, Iwate Medical University, Morioka, Japan
Yutaka Matsumura, Yohsuke Hirata, Tsuyoshi Metoki, Susumu Hayakawa, Yuichi Sato, Masayuki Takeda, Koichiro Sera & Kazunori Terasaki
Cyclotron Research Center, Iwate Medical University, Morioka, Japan
Toshiaki Sasaki
Nishina Memorial Cyclotron Center, Japan Radioisotope Association, Takizawa, Japan
Yoshihiro Saitoh & Shoko Goto
Departmetnt of Neurology, Research Institute for Brain and Blood Vessels-Akita, Akita, Japan
Ken Nagata, Yuichi Sato, Tetsuya Maeda, Yasushi Kondoh, Takashi Yamazaki, Daiki Takano, Mio Miyata, Hiromi Komatsu, Mayumi Watanabe, Tomomi Sinoda & Rena Muraoka
Pharmacy, Research Institute for Brain and Blood Vessels-Akita, Akita, Japan
Kayoko Kikuchi
Medical Support Department, Research Institute for Brain and Blood Vessels-Akita, Akita, Japan
Hitomi Ito & Aki Sato
Department of Radiology, Research Institute for Brain and Blood Vessels-Akita, Akita, Japan
Toshibumi Kinoshita, Hideyo Toyoshima, Kaoru Sato & Shigeki Sugawara
Clinical Laboratory, Research Institute for Brain and Blood Vessels-Akita, Akita, Japan
Isao Ito & Fumiko Kumagai
Geriatrics and Gerontology, Tohoku University Hospital, Sendai, Japan
Hiroyuki Arai, Katsutoshi Furukawa, Masaaki Waragai, Naoki Tomita, Mari Ootsuki, Katsumi Sugawara & Satomi Sugawara
Pharamacology, Tohoku University Hospital, Sendai, Japan
Nobuyuki Okamura
RadiologyTohoku University Hospital, Sendai, Japan
Shunji Mugikura, Atsushi Umetsu, Takanori Murata & Tatsuo Nagasaka
Neuroimaging, Tohoku University Hospital, Sendai, Japan
Yukitsuka Kudo
Nuclear Medicine, Tohoku University Hospital, Sendai, Japan
Manabu Tashiro & Shoichi Watanuki
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan
Masatoyo Nishizawa, Takeshi Ikeuchi & Takayoshi Tokutake
Department of Rehabilitation, Niigata University Medical and Dental Hospital, Niigata, Japan
Saeri Ishikawa, Emiko Kishida & Nozomi Sato
Clinical Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan
Mieko Hagiwara, Kumi Yamanaka, Takeyuki Watanabe & Taeko Takasugi
Department of Radiology, Niigata University Medical and Dental Hospital, Niigata, Japan
Shoichi Inagawa, Kenichi Naito, Masanori Awaji & Tsutomu Kanazawa
Department of Neurology, Gunma University Hospital, Maebashi, Japan
Kouiti Okamoto, Masaki Ikeda, Yuiti Tasiro, Syunn Nagamine & Sathiko Kurose
Department of Health of Rehabilitation, Gunma University Hospital, Maebashi, Japan
Tsuneo Yamazaki & Shiori Katsuyama
Clinical Trial Unit, Gunma University Hospital, Maebashi, Japan
Sayuri Fukushima & Etsuko Koya
Department of Radiology, Gunma University Hospital, Maebashi, Japan
Makoto Amanuma, Kouiti Ujita, Kazuhiro Kishi & Kazuhisa Tuda
Department of Nuclear Medicine Image, Gunma University Hospital, Maebashi, Japan
Noboru Oriuti
Department of Psychiatry Division of Clinical MedicineFaculty of Medicine, University of Tsukuba, Tsukuba, Japan
Takashi Asada, Katsuyoshi Mizukami, Tetsuaki Arai & Etsuko Nakajima
Department of Radiological Technology, Tsukuba Medical Center Hospital, Tsukuba, Japan
Katsumi Miyamoto, Tomoya Kobayashi, Saori Itoya, Jun Ookubo, Toshiya Akatsu, Yoshiko Anzai, Junya Ikegaki, Yuuichi Katou, Kaori Kimura, Hajime Saitou, Kazuya Shinoda, Satoka Someya, Hiroko Taguchi, Kazuya Tashiro, Masaya Tanaka, Tatsuya Nemoto, Ryou Wakabayashi & Daisuke Watanabe
Former Department of Radiological Technology, Tsukuba Medical Center Hospital, Tsukuba, Japan
Kousaku Saotome & Ryou Kuchii
Molecular Imaging Center Molecular Neuroimaging Program, National Institute of Radiological Sciences, Chiba, Japan
Harumasa Takano, Tetsuya Suhara, Hitoshi Shinoto, Hitoshi Shimada, Makoto Higuchi & Takaaki Mori
Molecular Imaging Center Biophysics Program, National Institute of Radiological Sciences, Chiba, Japan
Hiroshi Ito & Takayuki Obata
Molecular Imaging Center Planning and Promotion Unit Clinical Research Support Section, National Institute of Radiological Sciences, Chiba, Japan
Yoshiko Fukushima, Kazuko Suzuki & Izumi Izumida
Hospital Research Center for Charged Particle Therapy Radiological Technology Section, National Institute of Radiological Sciences, Chiba, Japan
Katsuyuki Tanimoto & Takahiro Shiraishi
Asahi Hospital for Neurological Diseases and Rehabilitation, Matsudo, Japan
Hitoshi Shinotoh, Hitoshi Shimada, Junko Shiba, Hiroaki Yano, Miki Satake, Aimi Nakui, Yae Ebihara & Tomomi Hasegawa
National Hospital Organization Chiba East National Hospital, Chiba, Japan
Yasumasa Yoshiyama, Mami Kato, Yuki Ogata & Hiroyuki Fujikawa
Department of Neurology & Stroke Care Unit, Saitama Medical University Hospital, Moroyama, Japan
Nobuo Araki, Yoshihiko Nakazato, Takahiro Sasaki, Tomokazu Shimadu & Kimiko Yoshimaru
Department of Nuclear Medicine, Saitama Medical University Hospital, Moroyama, Japan
Hiroshi Matsuda, Etsuko Imabayashi, Asako Yasuda & Keiko Ozawa
Department of Rehabilitation, Saitama Medical University Hospital, Moroyama, Japan
Etuko Yamamoto, Natsumi Nakamata & Noriko Miyauchi
Central Radiology Division, Saitama Medical University Hospital, Moroyama, Japan
Rieko Hashimoto, Taishi Unezawa, Takafumi Ichikawa, Hiroki Hayashi, Masakazu Yamagishi, Tunemichi Mihara, Masaya Hirano & Shinichi Watanabe
Pharmacy Division, Saitama Medical University Hospital, Moroyama, Japan
Junichiro Fukuhara & Hajime Matsudo
SHI Accelerator Service Ltd. (SAS), Tokyo, Japan
Nobuyuki Saito
Department of Neurology, The University of Tokyo Hospital, Tokyo, Japan
Atsushi Iwata, Hisatomo Kowa, Toshihiro Hayashi, Ryoko Ihara, Toji Miyagawa, Mizuho Yoshida, Yuri Koide, Eriko Samura & Kurumi Fujii
Clinical Research Center, The University of Tokyo Hospital, Tokyo, Japan
Kaori Watanabe & Nagae Orihara
Department of Nuclear Medicine, The University of Tokyo Hospital, Tokyo, Japan
Toshimitsu Momose, Miwako Takahashi, Takuya Arai & Yoshiki Kojima
Department of Diagnostic Radiology, The University of Tokyo Hospital, Tokyo, Japan
Akira Kunimatsu & Harushi Mori
Radiological Center, The University of Tokyo Hospital, Tokyo, Japan
Masami Goto, Takeo Sarashina, Syuichi Uzuki, Seiji Katou, Yoshiharu Sekine & Yukihiro Takauchi
Neuroscience, Faculty of Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Chiine Kagami
Department of Neurology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
Kazutomi Kanemaru, Yasushi Nishina, Maria Sakaibara, Yumiko Okazaki, Rieko Okada & Maki Obata
Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
Shigeo Murayama, Kenji Ishii & Masaki Takao
Clinical Support Corporation, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan
Yuko Iwata, Mizuho Minami, Yasuko Hanabusa, Hanae Shingyouji & Kyoko Tottori
Department of Radiology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
Aya Tokumaru, Makoto Ichinose, Kazuya Kume & Syunsuke Kahashi
Department of Psychiatry, National Center Hospital National Center of Neurology and Psychiatry, Kodaira, Japan
Kunimasa Arima, Shin Tanaka, Yuko Nagahusa, Masuhiro Sakata, Mitsutoshi Okazaki, Yuko Saito & Maki Yamada
Department of Neurology, National Center Hospital National Center of Neurology and Psychiatry, Kodaira, Japan
Tadashi Tukamoto
Administration Office of J-ADNI, National Center Hospital National Center of Neurology and Psychiatry, Kodaira, Japan
Tiine Kodama, Maki Obata, Tomoko Takeuchi & Keiichiro Ozawa
Clinical Support Corporation, National Center Hospital National Center of Neurology and Psychiatry, Kodaira, Japan
Yuko Iwata, Hanae Shingyouji, Yasuko Hanabusa, Yoshiko Kawaji & Kyouko Tottori
Department of Radiology, National Center Hospital National Center of Neurology and Psychiatry, Tokyo, Japan
Noriko Sato, Yasuhiro Nakata, Satoshi Sawada, Makoto Mimatsu, Daisuke Nakkamura, Takeshi Tamaru & Shunichirou Horiuchi
Juntendo University Hospital, Mental Clinic, Tokyo, Japan
Heii Arai, Tsuneyoshi Ota, Aiko Kodaka, Yuko Tagata & Tomoko Nakada
PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan
Eizo Iseki & Kiyoshi Sato
PET/CT Dementia Research Center, Department of Neuro-Psychiatry, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan
Hiroshige Fujishiro
Department of Neuro-Psychiatry, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan
Norio Murayama
Radiology, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan
Masaru Suzuki, Satoshi Kimura & Masanobu Takahashi
Department of Geriatric Medicine, Tokyo Medical University, Tokyo, Japan
Haruo Hanyu, Hirofumi Sakurai, Takahiko Umahara, Hidekazu Kanetaka, Kaori Arashino, Mikako Murakami & Ai Kito
Tokyo Medical University, Tokyo, Japan
Seiko Miyagi, Kaori Doi & Kazuyoshi Sasaki
Division of Neurology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
Mineo Yamazaki, Akiko Ishiwata, Yasushi Arai, Akane Nogami & Sumiko Fukuda
Clinical Support Corporation, Nippon Medical School Hospital, Japan
Kyouko Tottori, Mizuho Minami & Yuko Iwata
Geriatric Medicine, Kyorin University, Mitaka, Japan
Koichi Kozaki, Yukiko Yamada, Sayaka Kimura & Ayako Machida
Radiation Medicine, Kyorin University, Mitaka, Japan
Kuninori Kobayashi
Tokyo Medical and Dental University Graduate school of Medicine and Dental Sciences, Tokyo, Japan
Hidehiro Mizusawa, Nobuo Sanjo, Mutsufusa Watanabe, Takuya Ohkubo, Hiromi Utashiro, Yukiko Matsumoto, Kumiko Hagiya, Yoshiko Miyama, Hitoshi Shibuya, Isamu Ohashi & Akira Toriihara
Clinical Research Center, Tokyo Medical and Dental University Hospital Faculty of Medicine, Tokyo, Japan
Takako Shinozaki & Haruko Hiraki
Department of Radiology, Tokyo Medical and Dental University Hospital Faculty of Medicine, Tokyo, Japan
Shinichi Ohtani
Clinical Center for Neurodegenerative, National Hospital Organization Kurihama Medical & Addiction Center, Yokosuka, Japan
Toshifumi Matsui, Tomomi Toyama, Hideki Sakurai & Kumiko Sugiura
Department of Psychiatry, Kitasato University School of Medicine, Sagamihara, Japan
Yu Hayasaka
Department of Radiology, National Hospital Organization Kurihama Medical & Addiction Center, Yokosuka, Japan
Hirofumi Taguchi
Neurosurgery, Shonan-atsugi Hospital, Atsugi, Japan
Shizuo Hatashita
Clinical Research Center, Shonan-atsugi Hospital, Atsugi, Japan
Akari Imuta & Akiko Matsudo
Radiology, Shonan-atsugi Hospital, Atsugi, Japan
Daichi Wakebe, Hideki Hayakawa, Mitsuhiro Ono & Takayoshi Ohara
Department of Cognitive Disorders, National Center of Geriatrics and Gerontology, Obu, Japan
Yukihiko Washimi, Yutaka Arahata, Akinori Takeda, Akiko Yamaoka, Masashi Tsujimoto, Takiko Kawai & Ai Honda
Dementia Care Research and Training Center, National Center of Geriatrics and Gerontology, Obu, Japan
Yoko Konagaya
Department of Psychiatry, National Center of Geriatrics and Gerontology, Obu, Japan
Hideyuki Hattori, Kenji Yoshiyama & Rina Miura
Center for Comprehensive Care and Research on Memory Disorders, National Center of Geriatrics and Gerontology, Obu, Japan
Takashi Sakurai
Department of Home Medical Care Support, National Center of Geriatrics and Gerontology, Obu, Japan
Miura Hisayuki
Department of Comprehensive Geriatric Medicine, National Center of Geriatrics and Gerontology, Obu, Japan
Hidetoshi Endou
Department of Geriatrics, National Center of Geriatrics and Gerontology, Obu, Japan
Syousuke Satake & Young Jae Hong
Department of Neurology, National Center of Geriatrics and Gerontology, Obu, Japan
Katsunari Iwai, Masaki Suenaga & Sumiko Morita
Department of Clinical and Experimental Neuroimaging, National Center of Geriatrics and Gerontology, Obu, Japan
Kengo Itou, Takashi Kato & Ken Fujiwara
Department of Radiology, National Center of Geriatrics and Gerontology, Obu, Japan
Rikio Katou, Mariko Koyama, Naohiko Fukaya, Akira Tsuji, Hitomi Shimizu, Hiroyuki Fujisawa, Tomoko Nakazawa, Satoshi Koyama & Takanori Sakata
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
Masahito Yamada, Mitsuhiro Yoshita, Miharu Samuraki, Kenjiro Ono, Moeko Shinohara, Yuki Soshi, Kozue Niwa & Chiaki Doumoto
Center for Clinical Research Management, Kanazawa University Hospital, Kanazawa, Japan
Mariko Hata, Miyuki Matsushita & Mai Tsukiyama
The Medical and Pharmacological Research Center Foundation, Kanazawa, Japan
Nozomi Takeda, Sachiko Yonezawa & Ichiro Matsunari
Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
Osamu Matsui, Fumiaki Ueda & Yasuji Ryu
Department of Neurology, Hamamatsu Medical Center, Hamamatsu, Japan
Masanobu Sakamoto, Yasuomi Ouchi & Yumiko Fujita
Hamamatsu University School of Medicine, Hamamatsu, Japan
Yasuomi Ouchi
Hamamatsu Medical Center, Hamamatsu, Japan
Madoka Chita
Department of Psychiatry, Hamamatsu Medical Center, Hamamatsu, Japan
Rika Majima
Department of Clinical Research Management, Hamamatsu Medical Center, Hamamatsu, Japan
Hiromi Tsubota
Department of Radiological Technology, Hamamatsu Medical Center, Hamamatsu, Japan
Umeo Shirasawa, Masashi Sugimori, Wataru Ariya, Yuuzou Hagiwara & Yasuo Tanizaki
Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan
Hidenao Fukuyama, Shizuko Tanaka-Urayama & Shin-Ichi Urayama
Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Ryosuke Takahashi & Kengo Uemura
Department of Geriatric Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
Hajime Takechi
Eli Lilly Japan K.K Medical Science, Kobe, Japan
Chihiro Namiki
Rakuwakai Misasagi Hospital, Kyoto, Japan
Takeshi Kihara
Shiga Medical Center Research Institute, Moriyama, Japan
Hiroshi Yamauchi
Takemura Clinic, Kyoto, Japan
Emiko Maeda
Tonami General Hospital, Tonami, Japan
Natsu Saito
University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
Shiho Satomi
Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan
Konomi Kabata
Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
Tomohisa Okada
Department of Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan
Koichi Ishizu
Department of Radiology and Nuclear Medicine Service, Kyoto University Hospital, Kyoto, Japan
Shigeto Kawase & Satoshi Fukumoto
Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Masanori Nakagawa, Masaki Kondo, Fumitoshi Niwa, Toshiki Mizuno, Yoko Oishi, Mariko Yamazaki & Daisuke Yamaguchi
Department of Molecular Pathobiology of Brain Diseases (Department of Neurology), Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Takahiko Tokuda
Tokyo Yakuriken Co., Ltd, Tokyo, Japan
Kyoko Ito, Yoku Asano & Chizuru Hamaguchi
Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Kei Yamada, Chio Okuyama, Kentaro Akazawa & Shigenori Matsushima
Kyoto Prefectural University of Medicine Hospital, Kyoto, Japan
Takamasa Matsuo, Toshiaki Nakagawa, Takeshi Nii & Takuji Nishida
Department of Psychiatry, Nara Medical University, Kashihara, Japan
Kuniaki Kiuchi
Faculty of Psychology, Doshisha University, Kyotanabe, Japan
Masami Fukusumi
Heartland Shigisan Hospital, Sango, Japan
Hideyuki Watanabe
Department of Radiology, Nara Medical University, Kashihara, Japan
Toshiaki Taoka
Central Radiology, Nara Medical University, Kashihara, Japan
Akihiro Nogi
Psychiatry, Department of Integrated Medicine, Division of Internal Medicine, Osaka University Graduate School of Medicine, Suita, Japan
Masatoshi Takeda, Toshihisa Tanaka, Hiroaki Kazui, Kenji Yoshiyama, Takashi Kudo, Masayasu Okochi, Takashi Morihara, Shinji Tagami, Masahiko Takaya, Tamiki Wada, Mikiko Yokokoji, Hiromichi Sugiyama, Daisuke Yamamoto, Keiko Nomura & Mutsumi Tomioka
Department of Clinical Gene Therapy, Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan
Naoyuki Sato
Department of Complementary and Alternative Medicine, Osaka University Graduate School of Medicine, Suita, Japan
Noriyuki Hayashi
Japan Society for the Promotion of Science, Tokyo, Japan
Shuko Takeda
Uchida Clinic/Department of radiology, Osaka University Graduate School of Medicine, Ibaraki/Suita, Japan
Eiichi Uchida, Yoshiyuki Ikeda & Mineto Murakami
Department of Geriatrics and Neurology, Osaka City University Graduate School of Medicine, Osaka, Japan
Takami Miki, Hiroyuki Shimada, Suzuka Ataka, Akitoshi Takeda & Yuki Iwamoto
Osaka Municipal Kohsaiin Hospital, Suita, Japan
Motokatsu Kanemoto
Kishiwada City Hospital, Kishiwada, Japan
Jun Takeuchi
Department of Psychiatry, Kosaka Hospital, Higashiosaka, Japan
Rie Azuma
Osaka City University Hospital Center for Drug and Food Clinical Evaluation, Osaka, Japan
Naomi Tagawa, Junko Masao, Yuka Matsumoto, Yuko Kikukawa, Hisako Fujii & Junko Matsumura
Department of Nuclear Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
Susumu Shiomi & Joji Kawabe
Department of Radiology, Osaka City University Hospital, Osaka, Japan
Yoshihiro Shimonishi, Mitsuji Higashida, Tomohiro Sahara & Takashi Yamanaga
Department of Radiology, Osaka City University Graduate School of Medicine, Osaka, Japan
Yukio Miki & Shinichi Sakamoto
Department of Radiological Science, Ibaraki Prefectural University of Health Sciences, Ami, Japan
Hiroyuki Tsushima
Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan
Kiyoshi Maeda, Yasuji Yamamoto, Kazuo Sakai, Haruhiko Oda & Yoshihiko Tahara
Kobe University Graduate School of Health Sciences, Kobe, Japan
Toshio Kawamata
Department of General Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
Takashi Sakurai & Taichi Akisaki
Derartment of Psychiatry and Neurology, Kobe University Hospital, Kobe, Japan
Mizuho Adachi, Masako Kuranaga & Sachi Takegawa
Department of Psychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical, Okayama, Japan
Seishi Terada, Yuki Kishimoto, Naoya Takeda, Nao Imai, Mayumi Yabe & Reiko Wada
Department of Psychiatry, Kawasaki Hospital, Kurashiki, Japan
Takeshi Ishihara
Department of Psychiatry, Okayama University Hospital, Okayama, Japan
Hajime Honda & Osamu Yokota
Department of Imaging Diagnosis, Okayama Diagnostic Imaging Center, Okayama, Okayama, Japan
Kentaro Ida
Department of Imaging Technology, Okayama Diagnostic Imaging Center, Okayama, Okayama, Japan
Daigo Anami, Seiji Inoue & Toshi Matsushita
Department of Administration, Okayama Diagnostic Imaging Center, Okayama, Japan
Shinsuke Hiramatsu
Okayama University Hospital, Okayama, Japan
Hiromi Tonbara & Reiko Yamamoto
Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan
Kenji Nakashima, Kenji Wada-Isoe & Saori Yamasaki
Division of Clinical Radiology, Tottori University Hospital, Yonago, Japan
Eijiro Yamashita
Department of Neuropsychiatry Kagawa University School of Medicine, Kagawa, Japan
Yu Nakamura, Ichiro Ishikawa, Sonoko Danjo, Tomomi Shinohara & Yuka Kashimoto
Kagawa University Hospital Cancer center, Kagawa, Japan
Miyuki Ueno
Department of Radiology, Faculty of Medicine, Kagawa University, Kagawa, Japan
Yoshihiro Nishiyama, Yuka Yamamoto & Narihide Kimura
Department of Clinical Radiology, Kagawa University Hospital, Kagawa, Japan
Kazuo Ogawa, Yasuhiro Sasakawa, Takashi Ishimori & Yukito Maeda
Department of Neurology, Fukuoka University, Fukuoka, Japan
Tatsuo Yamada, Shinji Ouma & Aika Fukuhara-Kaneumi
Neues Corporation, Tokyo, Japan
Nami Sakamoto & Rie Nagao
Department of Radiology, Fukuoka University, Fukuoka, Japan
Kengo Yoshimitsu & Yasuo Kuwabara
Radiology Center, Fukuoka University Hospital, Fukuoka, Japan
Ryuji Nakamuta & Minoru Tanaka
Department of Psychiatry and Neuropathobiology, Faculty of Life Science, Kumamoto University, Kumamoto, Japan
Manabu Ikeda & Yuusuke Yatabe
Department of Neuropsychiatry, Kumamoto University Hospital, Kumamoto, Japan
Mamoru Hashimoto, Keiichirou Kaneda, Kazuki Honda, Naoko Ichimi, Mariko Morinaga & Miyako Noda
A Center of Support for Child Development, Kumamoto University Hospital, Kumamoto, Japan
Fumi Akatuka
Department of Medical Imaging, Kumamoto University, Kumamoto, Japan
Mika Kitajima
Department of Diagnostic Imaging, Faculty of Life Science, Kumamoto University, Kumamoto, Japan
Toshinori Hirai & Shinya Shiraishi
Department of Psychiatry, Shinshu University School of Medicine, Matsumoto, Japan
Naoji Amano, Shinsuke Washizuka, Tetsuya Hagiwara, Yatsuka Okada & Tomomi Ogihara
Department of Psychiatry, Shinshu University Hospital, Matsumoto, Japan
Toru Takahashi, Shin Inuzuka, Nobuhiro Sugiyama, Takehiko Yasaki, Minori Kitayama, Tomonori Owa & Akiko Ryokawa
Clinical Trial Research Center, Shinshu University Hospital, Matsumoto, Japan
Rie Takeuchi, Satoe Goto, Keiko Yamauchi & Mie Ito
Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan
Tomoki Kaneko
Radiology Division, Shinshu University Hospital, Matsumoto, Japan
Hitoshi Ueda
Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan
Shuichi Ikeda
Mihara Memorial Hospital, Isesaki, Japan
Masaki Takao, Ban Mihara, Hirofumi Kubo, Akiko Takano, Gou Yasui, Masami Akuzawa & Kaori Yamaguchi
Psychiatric Center, Yokohama City University Medical Center, Yokohama, Japan
Toshinari Odawara & Naomi Oota
Neurology, Yokohama City University Medical Center, Yokohama, Japan
Megumi Shimamura & Mikiko Sugiyama
Yokohama City University Medical Center, Yokohama, Japan
Atsushi Watanabe
Radiology, Yokohama City University Medical Center, Yokohama, Japan
Shigeo Takebayashi, Yoshigazu Hayakawa, Mitsuhiro Idegawa & Noriko Toya
Kindai University, Sayama, Japan
Kazunari Ishii
(2)
Francisco J. Garcia, Na Sun, Hyeseung Lee, Brianna Godlewski, Kyriaki Galani, Blake Zhou, Julio Mantero, David A. Bennett, Mustafa Sahin, Manolis Kellis & Myriam Heiman 
Single-cell dissection of the human brain vasculature
Nature (2022)
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Author information
Author notes
These authors contributed equally: Francisco J. Garcia, Na Sun
Affiliations
Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA
Francisco J. Garcia & Myriam Heiman
Picower Institute for Learning and Memory, Cambridge, MA, USA
Francisco J. Garcia, Hyeseung Lee, Blake Zhou & Myriam Heiman
Broad Institute of MIT and Harvard, Cambridge, MA, USA
Francisco J. Garcia, Na Sun, Hyeseung Lee, Kyriaki Galani, Blake Zhou, Julio Mantero, Manolis Kellis & Myriam Heiman
Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA, USA
Na Sun, Kyriaki Galani, Julio Mantero & Manolis Kellis
MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA
Na Sun, Kyriaki Galani, Julio Mantero & Manolis Kellis
Rosamund Stone Zander Translational Neuroscience Center, F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children’s Hospital, Boston, MA, USA
Brianna Godlewski & Mustafa Sahin
Department of Neurology, Harvard Medical School, Boston, MA, USA
Brianna Godlewski & Mustafa Sahin
Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA
David A. Bennett
(3)
Andrew C. Yang, Ryan T. Vest, Fabian Kern, Davis P. Lee, Maayan Agam, Christina A. Maat, Patricia M. Losada, Michelle B. Chen, Nicholas Schaum, Nathalie Khoury, Angus Toland, Kruti Calcuttawala, Heather Shin, Róbert Pálovics, Andrew Shin, Elizabeth Y. Wang, Jian Luo, David Gate, Walter J. Schulz-Schaeffer, Pauline Chu, Julie A. Siegenthaler, M. Windy McNerney, Andreas Keller & Tony Wyss-Coray 
A human brain vascular atlas reveals diverse mediators of Alzheimer’s risk
Nature (2022)
---
Author information
Author notes
These authors contributed equally: Ryan T. Vest, Fabian Kern
Affiliations
Department of Anatomy, University of California San Francisco, San Francisco, CA, USA
Andrew C. Yang & Michelle B. Chen
Bakar Aging Research Institute, University of California San Francisco, San Francisco, CA, USA
Andrew C. Yang & Tony Wyss-Coray
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA
Andrew C. Yang, Ryan T. Vest, Fabian Kern, Davis P. Lee, Maayan Agam, Christina A. Maat, Patricia M. Losada, Nicholas Schaum, Nathalie Khoury, Kruti Calcuttawala, Heather Shin, Róbert Pálovics, Andrew Shin, David Gate, Andreas Keller & Tony Wyss-Coray
Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany
Fabian Kern, Pauline Chu & Andreas Keller
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
Angus Toland
Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Elizabeth Y. Wang
Veterans Administration Palo Alto Healthcare System, Palo Alto, CA, USA
Jian Luo
Institute for Neuropathology, Saarland University Hospital and Medical Faculty of Saarland University, Homburg, Germany
Walter J. Schulz-Schaeffer
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Julie A. Siegenthaler
Department of Psychiatry, Stanford University School of Medicine, Stanford, CA, USA
M. Windy McNerney
Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA
Tony Wyss-Coray
Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA
Tony Wyss-Coray
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