Study of preclinical diagnosis and pre-emptive treatment trial for neurodegenerative dementia

• Project/Area Number: 15K09820
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Tohoku University
• Principal Investigator: Waragai Masaaki 東北大学, 加齢医学研究所, 非常勤講師 (50533775)
• Research Collaborator: 徳田 隆彦 京都府立医科大学, 大学院医学研究科分子脳病態解析学(神経内科), 教授 (80242692) ; 鈴木 利治 北海道大学, 薬学研究院, 教授 (80179233) ; 荒井 啓行 東北大学, 加齢医学研究所, 教授 (30261613)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: アルツハイマー病 / 血液バイオマーカーバイオマーカー / MRスペクトロスコピー / 後部帯状回 / 血液バイオマーカー / MRI / MRS / バイオマーカー / アルカデイン / アディポネクチン / パーキンソン病 / シヌクレイン / PMCA法 / 脳脊髄液 / 血清 / 神経原性変化 / タウ

Outline of Final Research Achievements

We studied early and easy diagnostic methods for Mild Cognitive Impairment(MCI) and Alzheimer's Disease(AD) using by blood based factors and usual 1.5T Magnetic Resonance Imaging(MRI) and spectroscopy(MRS) of the brain combined with cerebrospinal fluid(CSF) biomarkers amyloid beta and phosphorylated tau (p-tau) in clinical practice. We found that plasma p-tau level is significantly increased in patients with early AD and Down syndrome which have same brain pathology as AD. Thus, the plasma levels of p-tau may be used for good blood biomarker for screening subjects at risk of AD.
Furthermore, our longitudinal study of brain metabolites by MRS demonstrated that significant decreased N-acetylaspartate (NAA)/Myo-inositol(MI) ratio in the posterior cingulate gyri(PCG) not only in symptomatic AD but also preclinical AD.
Thus, we concluded that accurate measurement of plasma p-tau and amyloid beta together with decreased NAA/MI in the PCG could be used as useful peripheral AD biomarker.

Research Products

• [Int'l Joint Research] Department of Neurosciences,/University of California,/San Diego(米国)
• [Journal Article] Decreased N-Acetyl Aspartate/Myo-Inositol Ratio in the Posterior Cingulate Cortex Shown by Magnetic Resonance Spectroscopy May Be One of the Risk Markers of Preclinical Alzheimer's Disease: A 7-Year Follow-Up Study. (2017)
  • Author(s): Waragai M, Moriya M, Nojo T.
  • Journal Title: J Alzheimers Dis Volume: 60 Issue: 4 Pages: 1411-1427
  • DOI: 10.3233/jad-170450
  • Peer Reviewed / Open Access
• [Journal Article] Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case-control studies including patients with Alzheimer’s disease and down syndrome (2017)
  • Author(s): Tatebe Harutsugu、Kasai Takashi、Ohmichi Takuma、Kishi Yusuke、Kakeya Tomoshi、Waragai Masaaki、Kondo Masaki、Allsop David、Tokuda Takahiko
  • Journal Title: Molecular Neurodegeneration Volume: 12 Issue: 1 Pages: 1-11
  • DOI: 10.1186/s13024-017-0206-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Importance of adiponectin activity in the pathogenesis of Alzheimer's disease (2017)
  • Author(s): Waragai M, Ho G, Takamatsu Y, Sekiyama K, Sugama S, Takenouchi T, Masliah E, Hashimoto M
  • Journal Title: Ann Clin Transl Neurol Volume: 4 Issue: 8 Pages: 591-600
  • DOI: 10.1002/acn3.436
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Development of a Biochemical Diagnosis of Parkinson Disease by Detection of α-Synuclein Misfolded Aggregates in Cerebrospinal Fluid. (2017)
  • Author(s): Shahnawaz M, Tokuda T, Waragai M, Mendez N, Ishii R, Trenkwalder, Mollenhauer B, Soto C C,
  • Journal Title: JAMA Neurol Volume: 74 Issue: 2 Pages: 163-172
  • DOI: 10.1001/jamaneurol.2016.4547
  • Peer Reviewed / Open Access
• [Journal Article] Insight into the dissociation of behavior from histology in Synucleinopathies and in related neurodegenerative diseases (2016)
  • Author(s): Sekiyama K, Takamatsu Y, Koike W, Waragai M, Takenouchi T, Sugama S, Hashimoto M.
  • Journal Title: Journal of Alzheimer's Disease Volume: in press Issue: 3 Pages: 831-841
  • DOI: 10.3233/jad-151015
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Possible Involvement of Adiponectin, the Anti-Diabetes Molecule, in the Pathogenesis of Alzheimer’s Disease. (2016)
  • Author(s): Waragai M, Adame A, Trinh I, Sekiyama K, Takamatsu Y, Une K, Masliah E, Hashimoto M
  • Journal Title: J Alzheimers Dis. Volume: in press Issue: 4 Pages: 1453-1459
  • DOI: 10.3233/jad-151116
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of dementia by acrolein, amyloid-β and creatinine. (2015)
  • Author(s): Igarashi K, Yoshida M, Waragai M, Kashiwagi K
  • Journal Title: Clin Chim Acta Volume: 450 Pages: 56-63
  • DOI: 10.1016/j.cca.2015.07.017
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Abnormalities of MRS of the Posterior Cingulate Cortex May Precede onset of MCI Due to Alzheimer’s Diseases -Five Years Follow up Study of 277 Cognitive Normal Elderly Subjects- (2017)
  • Author(s): Masaaki Waragai, Masaru Moriya
  • Organizer: Alzheimer’s Association International Conference
  • Int'l Joint Research
• [Presentation] 日常診療でのVSRAD及びMRSを用いたアルツハイマー病の早期スクリーニングの有用性 (2015)
  • Author(s): 藁谷正明
  • Organizer: 第34回日本認知症学会学術集会
  • Place of Presentation: リンクステーションホール青森 第4会場、青森県、青森市
  • Year and Date: 2015-10-02
  • Invited
• [Presentation] Disease Modifying Effect of Adiponectin in Model of a-Synucleinopathies in Vitro and in Vivo (2015)
  • Author(s): Masaaki Waragai, Kazunari Sekiyama, Yoshiki Takamatsu, Masayo FujitaAkio Sekigawa, Naomichi Iwai , Edward Rockenstein , Satoshi Inoue, Albert R. La Spada, Elizer Masliah, Makoto Hashimoto
  • Organizer: Alzheimer's Association International Conference (AAIC2015)
  • Place of Presentation: Washington, DC United States
  • Year and Date: 2015-07-18
  • Int'l Joint Research