Blood biomarker for differentiating geriatric depression from Alzheimer's disease

• Project/Area Number: 18K07564
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Ehime University
• Principal Investigator: Iga Junichi 愛媛大学, 医学系研究科, 准教授 (70363140)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: うつ病 / 高齢者 / アルツハイマー型認知症 / レビー小体型認知症 / パーキンソン病 / バイオマーカー / 血液 / 遺伝子発現 / 老年期うつ病 / 統合失調症 / 認知症 / 鑑別

Outline of Final Research Achievements

To search for blood biomarkers to differentiate between geriatric depression (GD) and Alzheimer's disease (AD), we analyzed human blood, hippocampus and blood of AD model mice. We identified altered gene expression of MEF2C, Ghrelin, and PICALM in the blood of AD patients. On the other hand, PICALM was not altered in GD, which may be a useful marker for differentiation. In the microarray study using model mice, the human blood biomarkers that we have identified were also confirmed in mouse blood. We found that CDKN2A, which is involved in cellular senescence, was significantly altered in both blood and hippocampal tissues, and CDKN2A was also not altered in GD, which may be useful for differentiating AD from GD (submitted).

Academic Significance and Societal Importance of the Research Achievements

老年期うつ病とアルツハイマー型認知症は治療法も予後も異なる鑑別すべき疾患であるが、実臨床においては症状から鑑別は困難であり、早期に適切な治療が行えないことが多い。またGDからADに移行する症例も多く、両疾患の鑑別に役立つバイオマーカーの確立が望まれている。本研究からヒト血液の遺伝子発現やDNAメチル化率が各疾患の診断および鑑別のマーカーになりうることを証明した。モデルマウスの結果からは免疫や炎症に関わる遺伝子がマーカーとして特に有望であることが考察された。今後は大規模なサンプルで本研究結果の妥当性を検討する必要がある。

Research Products

• [Journal Article] Neural precursor cells are decreased in the hippocampus of the delayed carbon monoxide encephalopathy rat model (2021)
  • Author(s): Ochi S, Sekiya K, Abe N, Funahashi Y, Kumon H, Yoshino Y, Nishihara T, Boku S, Iga J, Ueno S
  • Journal Title: Scientific Reports Volume: 18 Issue: 1 Pages: 6244-6244
  • DOI: 10.1038/s41598-021-85860-9
  • Peer Reviewed / Open Access
• [Journal Article] PICALM mRNA Expression in the Blood of Patients with Neurodegenerative Diseases and Geriatric Depression (2021)
  • Author(s): Kumon Hiroshi、Yoshino Yuta、Funahashi Yu、Mori Hiroaki、Ueno Mariko、Ozaki Yuki、Yamazaki Kiyohiro、Ochi Shinichiro、Mori Takaaki、Iga Jun-ichi、Nagai Masahiro、Nomoto Masahiro、Ueno Shu-ichi
  • Journal Title: Journal of Alzheimer's Disease Volume: 79 Issue: 3 Pages: 1055-1062
  • DOI: 10.3233/jad-201046
  • Peer Reviewed / Open Access
• [Journal Article] Identifying Blood Transcriptome Biomarkers of Alzheimer’s Disease Using Transgenic Mice (2020)
  • Author(s): Ochi Shinichiro、Iga Jun-ichi、Funahashi Yu、Yoshino Yuta、Yamazaki Kiyohiro、Kumon Hiroshi、Mori Hiroaki、Ozaki Yuki、Mori Takaaki、Ueno Shu-ichi
  • Journal Title: Molecular Neurobiology Volume: 57 Issue: 12 Pages: 4941-4951
  • DOI: 10.1007/s12035-020-02058-2
  • Peer Reviewed / Open Access
• [Journal Article] Prevalence of possible idiopathic normal pressure hydrocephalus in older inpatients with schizophrenia: a replication study (2020)
  • Author(s): Yoshino Yuta、Yoshida Taku、Morino Hideo、Nakamura Masayuki、Abe Masao、Omachi Hokuto、Inoue Saori、Miyoshi Yukiyo、Tachibana Yumina、Yamauchi Noriko、Takeda Naoya、Mizobuchi Mutsuhiko、Ozaki Yuki、Ochi Shinichiro、Iga Junichi、Ueno Shu-ichi
  • Journal Title: BMC Psychiatry Volume: 20 Issue: 1 Pages: 273-273
  • DOI: 10.1186/s12888-020-02690-1
  • Peer Reviewed / Open Access
• [Journal Article] CTLA4 mRNA expression in blood is lower in schizophrenia, but not in affective disorders (2020)
  • Author(s): Miyamoto Keisuke、Funahashi Yu、Yoshino Yuta、Kawabe Kentaro、Yamazaki Kiyohiro、Ozaki Yuki、Mori Yoko、Ochi Shinichiro、Iga Jun-ichi、Ueno Shu-ichi
  • Journal Title: Asian Journal of Psychiatry Volume: 52 Pages: 102112-102112
  • DOI: 10.1016/j.ajp.2020.102112
  • Peer Reviewed / Open Access
• [Journal Article] Discontinuation of antidepressants after remission with antidepressant medication in major depressive disorder: a systematic review and meta-analysis (2020)
  • Author(s): Kato Masaki、Hori Hikaru、Inoue Takeshi、Iga Junichi、Iwata Masaaki、Inagaki Takahiko、Shinohara Kiyomi、Imai Hissei、Murata Atsunobu、Mishima Kazuo、Tajika Aran
  • Journal Title: Molecular Psychiatry Volume: 26 Issue: 1 Pages: 118-133
  • DOI: 10.1038/s41380-020-0843-0
  • Peer Reviewed / Open Access
• [Journal Article] Unmet needs of patients with major depressive disorder ? Findings from the ‘Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)’ project: A nationwide dissemination, education, and evaluation study (2020)
  • Author(s): Iida Hitoshi、Iga Junichi、Hasegawa Naomi、（45番目）Fujimoto Michiko、et al.
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 74 Issue: 12 Pages: 667-669
  • DOI: 10.1111/pcn.13143
  • Peer Reviewed / Open Access
• [Journal Article] Prescription patterns in patients with schizophrenia in Japan: First-quality indicator data from the survey of "Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)" project (2020)
  • Author(s): Ichihashi K, Hori H, Hasegawa N, Yasuda Y, Yamamoto T, Tsuboi T, Iwamoto K, Kishimoto T, Horai T, Yamada H, Sugiyama N, Nakamura T, Tsujino N, Nemoto K, Oishi S, Usami M, Katsumoto E, Yamamori H, Tomita H, Suwa T, Furihata R, Inagaki T, Fujita J, Onitsuka T, Miura K, Matsumoto J, Ohi K, Matsui Y, Takaesu Y, et al.
  • Journal Title: Neuropsychopharmacol Rep. Volume: 40 Issue: 3 Pages: 281-286
  • DOI: 10.1002/npr2.12122
  • Peer Reviewed / Open Access
• [Journal Article] 高齢者の薬物動態と治療反応性 (2020)
  • Author(s): 伊賀 淳一 , 熊ノ郷 頼之 , 辻川 真緒 , 岡山 さくら , 野津 佑真 , 上野 修一
  • Journal Title: Depression strategy : うつ病治療の新たなストラテジー Volume: 10 Pages: 4-6
  • NAID: 40022463175
• [Journal Article] (特集 精神科診療のエビデンス : 国内外の重要ガイドライン解説) -- (うつ病) (2020)
  • Author(s): 伊賀淳一
  • Journal Title: 精神医学 Volume: 62 Pages: 555-558
  • NAID: 40022236977
• [Journal Article] 教育講演 スポーツを日々のうつ病診療にどう生かすか? (第17回日本スポーツ精神医学会特集) (2020)
  • Author(s): 伊賀淳一
  • Journal Title: スポーツ精神医学 Volume: 17 Pages: 6-11
  • NAID: 40022336192
• [Journal Article] <p>ABCA7 Gene Expression and Genetic Association Study in Schizophrenia</p> (2020)
  • Author(s): Yamazaki Kiyohiro、Yoshino Yuta、Kawabe Kentaro、Ibuki Tomomasa、Ochi Shinichiro、Mori Yoko、Ozaki Yuki、Numata Shusuke、Iga Jun-ichi、Ohmori Tetsuro、Ueno Shu-ichi
  • Journal Title: Neuropsychiatric Disease and Treatment Volume: Volume 16 Pages: 441-446
  • DOI: 10.2147/ndt.s238471
  • NAID: 120006999410
  • Peer Reviewed / Open Access
• [Journal Article] Differential expression of the ghrelin-related mRNAs GHS-R1a, GHS-R1b, and MBOAT4 in Japanese patients with schizophrenia (2019)
  • Author(s): Nakata Shunsuke、Yoshino Yuta、Okita Mitsuo、Kawabe Kentaro、Yamazaki Kiyohiro、Ozaki Yuki、Mori Yoko、Ochi Shinichiro、Iga Jun-ichi、Ueno Shu-ichi
  • Journal Title: Psychiatry Research Volume: 272 Pages: 334-339
  • DOI: 10.1016/j.psychres.2018.12.135
  • Peer Reviewed
• [Journal Article] Dose-Dependent Efficacy of Tandospirone for an Oldest-Old Patient With Behavioral and Psychological Symptoms of Dementia (2019)
  • Author(s): Ochi Shinichiro、Mori Takaaki、Iga Jun-ichi、Ueno Shu-ichi
  • Journal Title: Journal of Clinical Psychopharmacology Volume: 39 Issue: 2 Pages: 176-178
  • DOI: 10.1097/jcp.0000000000000998
  • Peer Reviewed
• [Journal Article] Analysis of methylation and -141C Ins/Del polymorphisms of the dopamine receptor D2 gene in patients with schizophrenia (2019)
  • Author(s): Funahashi Yu、Yoshino Yuta、Yamazaki Kiyohiro、Ozaki Yuki、Mori Yoko、Mori Takaaki、Ochi Shinichiro、Iga Jun-ichi、Ueno Shu-ichi
  • Journal Title: Psychiatry Research Volume: 278 Pages: 135-140
  • DOI: 10.1016/j.psychres.2019.06.001
  • Peer Reviewed
• [Journal Article] Improvement of psychiatrists’ clinical knowledge of the treatment guidelines for schizophrenia and major depressive disorders using the “Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE) ” project: a nationwide dissemination, education and evaluation study. (2019)
  • Author(s): Takaesu Y, Watanabe K, (44名中略） Inada K, Hashimoto R.
  • Journal Title: Psychiatry Clin Neurosci Volume: 73(10) Issue: 10 Pages: 642-648
  • DOI: 10.1111/pcn.12911
  • NAID: 120007029981
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of Asenapine in Schizophrenia Resistant to Clozapine Combined with Electroconvulsive Therapy: A Case Report (2019)
  • Author(s): Ochi Shinichiro、Inoue Saori、Yoshino Yuta、Shimizu Hideaki、Iga Jun-ichi、Ueno Shu-ichi
  • Journal Title: Clinical Psychopharmacology and Neuroscience Volume: 17 Issue: 4 Pages: 559-563
  • DOI: 10.9758/cpn.2019.17.4.559
  • Peer Reviewed
• [Journal Article] DRD2 methylation to differentiate dementia with Lewy bodies from Parkinson's disease (2019)
  • Author(s): Ozaki Yuki、Yoshino Yuta、Yamazaki Kiyohiro、Ochi Shinichiro、Iga Jun‐ichi、Nagai Masahiro、Nomoto Masahiro、Ueno Shu‐ichi
  • Journal Title: Acta Neurologica Scandinavica Volume: 141 Issue: 2 Pages: 177-182
  • DOI: 10.1111/ane.13186
  • Peer Reviewed
• [Journal Article] Ghrelin cascade changes in the peripheral blood of Japanese patients with Alzheimer's disease (2018)
  • Author(s): Yoshino Yuta、Funahashi Yu、Nakata Shunsuke、Ozaki Yuki、Yamazaki Kiyohiro、Yoshida Taku、Mori Takaaki、Mori Yoko、Ochi Shinichiro、Iga Jun-ichi、Ueno Shu-ichi
  • Journal Title: Journal of Psychiatric Research Volume: 107 Pages: 79-85
  • DOI: 10.1016/j.jpsychires.2018.10.011
  • Peer Reviewed
• [Journal Article] TREM1 mRNA Expression in Leukocytes and Cognitive Function in Japanese Patients with Alzheimer’s Disease (2018)
  • Author(s): Sao Tomoko、Yoshino Yuta、Yamazaki Kiyohiro、Ozaki Yuki、Mori Yoko、Ochi Shinichiro、Yoshida Taku、Mori Takaaki、Iga Jun-Ichi、Ueno Shu-Ichi
  • Journal Title: Journal of Alzheimer's Disease Volume: 64 Issue: 4 Pages: 1275-1284
  • DOI: 10.3233/jad-180418
  • Peer Reviewed
• [Presentation] 統合失調症の緊張病 (2020)
  • Author(s): 伊賀淳一
  • Organizer: 第１１６回日本精神神経学会総会
• [Presentation] DRD2 methylation to differentiate dementia with Lewy bodies from Parkinson’s disease (2020)
  • Author(s): Junichi Iga, Yuki Ozaki, Yuta Yoshino, Kiyohiro Yamazaki, Shinicihro Ochi, Masahiro Nagai, Masahiro Nomoto, Shu-ichi Ueno
  • Organizer: NPBPPP 2020 合同年会
• [Presentation] Identifying blood transcriptome biomarkers of Alzheimer’s disease using transgenic mice. (2020)
  • Author(s): Jun-ichi Iga, Shinichiro Ochi, Yu Funahashi, Yuta Yoshino, Kiyohiro Yamazaki, Hiroshi Kumon, Hiroaki Mori, Yuki Ozaki, Takaaki Mori and Shu-ichi Ueno
  • Organizer: 第６３回日本神経化学会大会
• [Presentation] Ghrelin cascade changes in the peripheral blood of Japanese patients with Alzheimer’s disease (2019)
  • Author(s): Jun-ichi Iga, Yuta Yoshino, Yu Funahashi, Shunsuke Nakata, Yuki Ozaki, Kiyohiro Yamazaki, Taku Yoshida, Takaaki Mori, Yoko Mori, Shinichiro Ochi and Shu-ichi Ueno
  • Organizer: 6th Congress of AsCNP
  • Int'l Joint Research
• [Presentation] 5-HT1A partial agonist tandospirone for behavioral and psychological symptoms in oldest-old patients with dementia in a specialized elderly nursing home (2019)
  • Author(s): Shin-ichiro Ochi, Aya Santa, Takaaki Mori, Jun-ichi Iga and Shu-ichi Ueno
  • Organizer: 6th Congress of AsCNP
  • Int'l Joint Research
• [Presentation] TREM1 mRNA expression in leukocytes and cognitive function in Japanese patients with Alzheimer's disease (2019)
  • Author(s): Jun-ichi Iga, Tomoko Sao, Yuta Yoshino, Kiyohiro Yamazaki, Yuki Ozaki, Yoko Mori, Shinichiro Ochi, Taku Yoshida, Takaaki Mori and Shu-ichi Ueno.
  • Organizer: Neuroscience 2019
  • Int'l Joint Research
• [Presentation] Decreased neural precursor cells and glial cells in the hippocampus with delayed carbon monoxide encephalopathy (2019)
  • Author(s): Shin-ichiro Ochi, Keisuke Sekiya, Naoki Abe, Yu Nishihara, Jun-ichi Iga, and Shu-ichi Ueno
  • Organizer: Neuroscience 2019
  • Int'l Joint Research
• [Presentation] Analysis of methylation and -141C Ins/Del polymorphisms of the dopamine receptor D2 gene in patients with schizophrenia (2019)
  • Author(s): Funahashi Y, Yoshino Y, Yamazaki K, Ochi S, Iga J, Ueno S.
  • Organizer: Neuroscience 2019
  • Int'l Joint Research
• [Presentation] 超高齢化地域における認知昭の実態調査―大規模認知症コホート研究 中山町調査― (2019)
  • Author(s): 立花亜由美、吉田卓、森崇明、尾﨑優樹、山崎聖広、吉野祐太、森蓉子、河邉憲太郎、越智紳一郎、安部賢郎、清水秀明、堀内史枝、小森憲治郎、伊賀淳一、上野修一
  • Organizer: 第34回日本老年精神医学会
• [Presentation] -141C Ins / Del多型および末梢血白血球でのプロモーター領域DNAメチル化からDRD2 遺伝子と統合失調症の関連を解析する (2019)
  • Author(s): 舟橋 裕、吉野 祐太、山崎 聖広、尾崎 優樹、森 蓉子、森 崇明、越智 紳一郎、伊賀 淳一、上野 修一
  • Organizer: 第41回日本生物学的精神医学会
• [Presentation] うつ病治療ガイドラインアップデート 高齢者のうつ病治療ガイドラインの紹介 (2019)
  • Author(s): 伊賀淳一
  • Organizer: 第17回日本うつ病学会
• [Presentation] スポーツを日々のうつ病診療にどう生かすか? (2019)
  • Author(s): 伊賀淳一
  • Organizer: 第17回日本スポーツ精神医学会
• [Presentation] 高齢者の精神疾患に対する薬物療法Up-to-Date 精神病症状を伴う高齢者のうつ病の薬物療法 (2019)
  • Author(s): 伊賀淳一
  • Organizer: 第29回日本臨床精神神経薬理学会
• [Presentation] INPP5D mRNA expression and cognitive decline in Japanese Alzheimer’s disease subjects (2018)
  • Author(s): Jun-ichi Iga, Yuta Yoshino, Kiyohiro Yamazaki, Yuki Ozaki, Tomoko Sao, Taku Yoshida, Takaaki Mori, Yoko Mori, Shinichiro Ochi and Shu-ichi Ueno
  • Organizer: WFSBP2018KOBE
  • Int'l Joint Research
• [Presentation] TOMM40 & APOE gene expression and cognitive decline in Japanese Alzheimer’s disease subjects (2018)
  • Author(s): Jun-ichi Iga, Ayano Mise, Yuta Yoshino, Kiyohiro Yamazaki, Yuki Ozaki, Tomoko Sao, Taku Yoshida, Takaaki Mori, Yoko Mori, Shinichiro Ochi and Shu-ichi Ueno.
  • Organizer: Neuroscience 2018
  • Int'l Joint Research
• [Remarks] 愛媛大学大学院 精神神経科学
  • URL: https://www.m.ehime-u.ac.jp/school/neuropsychiatry/
• [Remarks] 愛媛大学大学院医学系研究科 精神神経科学講座
  • URL: https://www.m.ehime-u.ac.jp/school/neuropsychiatry/
• [Remarks] ORCID
  • URL: https://orcid.org/0000-0003-4409-3096
• [Remarks] Publon
  • URL: https://publons.com/researcher/1257681/jun-ichi-iga/
• [Remarks] 愛媛大学大学院医学系研究科精神神経科学講座
  • URL: https://www.m.ehime-u.ac.jp/school/neuropsychiatry/