Clinical study of preclinical useful diagnosis of Alzheimer's Disease using by MRI and periperal biomarkers

• Project/Area Number: 24591695
• 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)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: アルツハイマー病 / バイオマーカー / 神経変性疾患 / MRI / MRS / MRI-VSRAD / アルカデイン / 血漿中p3-Alc35 / 髄液中AB42 / 髄液中リン酸化タウ / VBM-MRI

Outline of Final Research Achievements

We studied methods of early diagnosis for Alzheimer's Disease(AD)/Mild Cognitive Impairment(MCI).We showed that MRI using by VSRAD　combined with MRS(magnetic resonance spectroscopy) of the brain is useful for early diagnosis and tracking progression of AD.　We found acrolein, a product of lipid peroxidation related factors are changed in the biofluids in MCI/AD. Furthermore, we also showed plasma p3-Alcα35, a mojor fragment of Alcadeinα by γ-secretase clevage are increased in AD suggesting plasma p3-Alcα35 could be good biomarker for MCI/AD.
Thus, we found potentially useful peripheral biomarkers and demonstrated MRI/MRS are useful for screening of AD in clinical practice.

Research Products

• [Journal Article] Distinguishing mild cognitive impairment from Alzheimer’s disease with acrolein metabolites and creatinine in urine. (2015)
  • Author(s): Yoshida, M. et al.
  • Journal Title: Clin. Chim. Acta Volume: 441 Pages: 115-121
  • DOI: 10.1016/j.cca.2014.12.023
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increased levels of plasma p3-Alcα35, a major fragment of Alcadeinα by γ-secretase cleavage, in Alzheimer's disease (2014)
  • Author(s): Omori C, Kaneko M, Nakajima E, Akatsu H, Waragai M, Maeda M, Moroshima-Kawashima M, Saito Y, Nakaya T, Taru H, Yamamoto T, Asada T, Hata S, Suzuki T. for J-ADNI
  • Journal Title: J. Alzheimers Dis Volume: 39 Issue: 4 Pages: 861-870
  • DOI: 10.3233/jad-131610
  • Peer Reviewed
• [Journal Article] Distinction between mild cognitive impairment and Alzhemer’s disease by CSF amyloid beta40 and beta42, and protein-conjugated acrolein. (2014)
  • Author(s): Mizoi, M. et al.
  • Journal Title: Clin. Chim. Acta Volume: 430 Pages: 150-155
  • DOI: 10.1016/j.cca.2014.01.007
  • Peer Reviewed
• [Journal Article] Utility of SPM8 plus DARTEL (VSRAD) combined with magnetic resonance spectroscopy as adjunct techniques for screening and predicting dementia due to Alzheimer’s disease in clinical practice. (2014)
  • Author(s): Waragai, M. et al.
  • Journal Title: J. Alzheimer’s Dis. Volume: 41 Issue: 4 Pages: 1207-1222
  • DOI: 10.3233/jad-132786
  • Peer Reviewed
• [Journal Article] Increased protein-conjugated acrolein and amyloid-40/42 ratio in plasma of patients with mild cognitive impairment and Alzheimer’s disease. (2012)
  • Author(s): Waragai, M.
  • Journal Title: J. Alzheimer’s Dis. Volume: 32 Issue: 1 Pages: 33-41
  • DOI: 10.3233/jad-2012-120253
  • Peer Reviewed
• [Journal Article] Ibuprofen ameliorates protein aggregation and astrocytic gliosis, but not cognitive dysfunction, in a transgenic mouse expressing dementia with Lewy bodies-linked P123H β-synuclein. (2012)
  • Author(s): Sekiyama K, Fujita M, Sekigawa A, Takamatsu Y, Waragai M, Takenouchi T, Sugama S, Hashimoto M.
  • Journal Title: Neurosci Lett. Volume: 515 Pages: 97-101
  • Peer Reviewed
• [Presentation] SPM8 plus DARTEL (VSRAD) combined with magnetic resonance spectroscopy are useful for screening and predicting dementia due to Alzheimer's disease in clinical practice. (2014)
  • Author(s): Masaaki Waragai, Saori Hata, Toshiharu Suzuki, Hiroyuki Arai, Takashi Ohrui, Masaru Moriya, Takeshi Yamamoto, Naomichi Iwai, Kenichi Uemura
  • Organizer: Alzheimer’s Association International Conference(AAIC) 2014, July 12-17
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2014-07-15
• [Presentation] VBM-MRI by SPM8 plus DARTEL combined with Magenetic Resonance Spectroscopy of the bilateral posterior gyri is useful for early diagnosis and tracking for Mild Cognitive Impairment and Alzheimer's disease . (2013)
  • Author(s): Masaaki Waragai, Saori Hata, Toshiharu Suzuki, Ryotaro Ishii, Chihiro Fujii, Takahiko Tokuda, Hiroyuki Arai, Takashi Ohrui, Susumu Higuchi, Madoka Yoshida, Kazuei Igarashi, Masaru Moriya, Naomichi Iwai, Kenichi Uemura
  • Organizer: Alzheimer‘s Association International Conference, Boston
  • Place of Presentation: Boston, USA
• [Presentation] Increased protein-conjugated acrolein and amyloid-β 40/42 ratio in plasma from patients with mild cognitive impairment and Alzheimer’s disease. (2012)
  • Author(s): Waragai M, Yoshida M, Mizoi M, Saiki R, Kashiwagi K, Takagi K, Arai H, Akatsu H, Tashiro J , Hashimoto M , Iwai N , Uemura K , Igarashi K
  • Organizer: Alzheimer‘s Association International Conference 2012
  • Place of Presentation: Vancouver, Canada