PET n = 7 AD n = 20 図 3 PiB AD A 3. わが国のアミロイド PET の現状 PET 100 PiB 15 BF 図 4 J-ADI 105 図 5 20%MCI 60% AD 90% MCI AD AD E ApoE 4 AD 4 図 6 4.

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病態理解と薬剤開発におけるアミロイド PET 検査の現状 Current Status of Amyloid PET in Pathophysiological Research and Drug Development for Alzheimer s Disease 東京都健康長寿医療センター研究所附属診療所 / 所長 * 1. はじめに PET A A AD 図 1 AD AD PET 2.

1 病態理解と薬剤開発におけるアミロイド PET 検査の現状 Current Status of Amyloid PET in Pathophysiological Research and Drug Development for Alzheimer s Disease 東京都健康長寿医療センター研究所附属診療所 / 所長 * 1. はじめに PET A A AD 図 1 AD AD PET 2. アミロイド PET 診断薬の開発 PET 図 2 T Pittsburgh Compound-B PiB PiB C 110 PiB 図 3 + S Tioflavin-T H2 S3a Congo Red H2 S3a 図 C C [ ]FDDP S H H [ 11 C]PiB 11 S [ 11 C]BF-227 F H [ ]AV-1 / BAY S H H [ ]3 F-PIB / AH H [ ]AV-45 図 2 Amyloid Probes for Human PET Study * Kenji Ishii, Head : Positron Medical Center, Tokyo Metropolitan Institute of Gerontology

PET n = 7 AD n = 20 図 3 PiB 50-70 AD A 3.

アミロイド PET の臨床的意義 PET 図 7 AD Fotenos 図 8 AD AD BF-227 4 Sites PIB ADI PIB non-adi BF ADI BF non-adi MHLW MPRCF, Hakui

ishijin Hsp, Kyoto Moro Chiba MinokamoTokyo IBRI, Kobe Kobe Kyoto bu Atsugi agoya Kagawa Univ Takamatsu saka Hamamatsu

Tokyo Univ IRS, Chiba TMIG Tokyo Shonan Atsugi Clinic Hamamatsu Univ 図 4 PET Cut off 1.

2 PET n = 7 AD n = 20 図 3 PiB AD A 3. わが国のアミロイド PET の現状 PET 100 PiB 15 BF 図 4 J-ADI 105 図 5 20%MCI 60% AD 90% MCI AD AD E ApoE 4 AD 4 図 6 4. アミロイド PET の臨床的意義 PET 図 7 AD Fotenos 図 8 AD AD BF Sites PIB ADI PIB non-adi BF ADI BF non-adi MHLW MPRCF, Hakui Amyloid PET etwork in Japan As of April 2010 Tohoku Univ Kizawakinen, Minokamo Sendai ILS, bu Koriyama Hakui Maebashi ishijin Hsp, Kyoto Moro Chiba MinokamoTokyo IBRI, Kobe Kobe Kyoto bu Atsugi agoya Kagawa Univ Takamatsu saka Hamamatsu Fujimoto-Hayasuzu Hsp Miyakonojo MinamiTohoku Hsp saka City Univ agoya City Reha Hsp PiB 15 Sites Gunma Univ Saitama Univ Tokyo Univ IRS, Chiba TMIG Tokyo Shonan Atsugi Clinic Hamamatsu Univ 図 4 PET Cut off 1.47 As of Apr 4, 2010 図 5 Mean cortical PiB uptake: SUVR By group and visual diagnosis (%) 100% 100% 11/11 90% 9/10 14/14 50% 7/14 57% 8/14 10% 3/ n = 21 n = 28 n = 45 図 6 PiB positive (MCSUVR > 1.47) rate by group and ApoE4 cerebral amyloidosis

Probably yes 現時点でアミロイドイメージングを検診として実施することは時期尚早図 9 図 10 MCI AD

3 Vol Aβ Fotenos et al. Arch eurol 2008;65:113 図 7 PiB in Healthy Controls 図 8 PiB PiB 陽性健常者の検討の意義発症の危険因子および予防因子の探索将来的な早期介入発症予防へ PiB(+) = ADか? o preclinical AD cerebral β-amyloidosis PiB(-) ADか? Probably yes 現時点でアミロイドイメージングを検診として実施することは時期尚早図 9 図 10 MCI AD preclinical AD PET 図 9 MCI 60-70% AD MCI AD 図根本治療薬治験とアミロイド PET PET AD 図 11 bapineuzumab 図 12 PET 6. 各種脳疾患におけるアミロイド PET の意義 PET AD PET 図

PET Bapineuzumab Rinne J et al. Lancet eurology 9:363-372(2010) Jack et al.

AD における病態進展とバイオマーカー AD A PET A 1-42 tau FDG-PET MRI 図 14 8.

4 PET Bapineuzumab Rinne J et al. Lancet eurology 9: (2010) Jack et al. Brain 132: (2009) 図 11 PiB 図 12 Aβ (PiB, CSF Aβ) Tau (CSF tau) (FDG, MRI, 心理検査 ) 図 13 PiB Jack et al. Lancet eurol 2010;9:119 を改変図 14 7.AD における病態進展とバイオマーカー AD A PET A 1-42 tau FDG-PET MRI 図おわりに PET α 図 15 アミロイドイメージングと分子病理画像の今後診断的意義の確定長期追跡研究病理との対比 [F-18] 標識製剤の治験と普及根本治療薬の治療対象選択治療効果判定アミロイドイメージングは AD 理解の時間的座標軸アミロイドカスケードタウカスケードの修飾因子の探索 Aβ 蓄積から神経障害に至るプロセスのマーカ開発 Aβ 以外のタンパク蓄積の画像化タウ ( 神経原線維変化 ) α シヌクレイン ( レビー小体 ) TDP-43 TMIG PET CETER 図 15 文献 1 Ishii K.: Amyloid PET in Alzheimer research. Brain and nerve 2010; 62, Klunk WE, Engler H, ordberg A, et al.: Imaging brain amyloid in Alzheimer s disease with

5 Vol Pittsburgh Compound-B. Annals of neurology. 2004; 55, Klunk WE, Mathis CA.: The future of amyloid-beta imaging: a tale of radionuclides and tracer proliferation. Current opinion in neurology. 2008; 21, J-ADI PET. Medical ow. 2010; 67, Fotenos AF, Mintun MA, Snyder AZ, et al.: Brain volume decline in aging: evidence for a relation between socioeconomic status, preclinical Alzheimer disease, and reserve. Archives of neurology. 2008; 65, Jack CR, Jr., Lowe VJ, Weigand SD, et al.: Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer s disease: implications for sequence of pathological events in Alzheimer s disease. Brain. 2009; 132, Rinne J, Brooks DJ, Rossor M, et al.: 11 C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer s disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet neurology. 2010; 9, Jack CR, Jr., Albert MS, Knopman DS, et al.: Introduction to the recommendations from the ational Institute on Aging-Alzheimer s Association 7, Sperling RA, Aisen PS, Beckett LA, et al.: Toward defining the preclinical stages of Alzheimer s disease: Recommendations from the ational Institute on Aging-Alzheimer s Association 7, McKhann GM, Knopman DS, Chertkow H, et al.: The diagnosis of dementia due to Alzheimer s disease: Recommendations from the ational Institute on Aging-Alzheimer s Association 7, Albert MS, Dekosky ST, Dickson D, et al.: The diagnosis of mild cognitive impairment due to Alzheimer s disease: Recommendations from the ational Institute on Aging-Alzheimer s Association 7,

Vol.21 No AD Japanese-ADNI J-ADNI 2015 AMED AD NA-ADNI 400 AD AD 2. NA-ADNI 研究の主な成果 NA-ADNI 2004 NA-ADNI ADNI, ADNI-GO ADNI-2 phase

Vol.21 No AD Japanese-ADNI J-ADNI 2015 AMED AD NA-ADNI 400 AD AD 2. NA-ADNI 研究の主な成果 NA-ADNI 2004 NA-ADNI ADNI, ADNI-GO ADNI-2 phase アルツハイマー型認知症のバイオマーカーの現状と課題 Biochemical biomarkers for Alzheimer s disease: present status and awaiting solution 京都府立医科大学分子脳病態解析学 / 教授 * 1. はじめに 460 65 10 1 85 3 1 Alzheimer s disease AD 5 7 2500 AD 460