APOE遺伝子多型に着目した外傷性脳損傷によるアルツハイマー病発症機構の解明

以APOE基因多态性阐明脑外伤所致阿尔茨海默病的发病机制

• 批准号: 22K07549
• 负责人: 鈴木 一詩
• 金额: $ 2.66万
• 依托单位: National Defense Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22K07549/
• 关键词: アルツハイマー病; APOE; 外傷性脳損傷; アミロイドβ; タウ; APOE4

本研究の臨床研究部分につき、学内倫理員会に研究計画を提出し承認を得た。ベトナム戦争でのTBI既往のある退役軍人を対象とした、認知症及びPTSDの縦断的観察研究であるDepartment of Defense Alzheimer's Disease Neuroimaging Initiative (DOD-ADNI) 研究のデータベースの取得申請を提出し、所定の審査を経てデータを入手し解析に着手した。予備的解析では、Screening visitに369名が来院し、このうちAPOE遺伝型の情報があるのは274名であった。APOE ε4アレルの保持率は正常群85例で27.1%, PTSD群112例で23%, TBI群54例で32.5%, PTSDとTBIの合併群118例で25%と、TBI群でε４アレルの保持率が高かった。ε４アレル保持が認知機能予後に与える影響を検討するため、274例全例につき各種認知機能検査(MMSE, MOCA, ADAS-cog13, Logical memory, Boston naming test, カテゴリー流暢性、時計描画、時計模写、トレイルメイキングテスト、RAVLT)および臨床評価指標（CDR-SB、GDS、NPI）の得点をε4保持群(n=72)とε4非保持群(n=202)間で比較したところ、RAVLTの総得点に有意差を認めた。さらにTBI受傷の影響を検討するため、TBI群(TBI単独群とTBIとPTSD合併群)124名に限定してε4保持群(n=34)とε4非保持群(n=90)間の比較を行ったが、総点に有意な得点差のある項目は認めなかった。また本研究の動物実験部分については、動物実験計画を防衛医大内の動物実験倫理審査委員会に提出し承認を得た。遺伝子改変動物を用いるため組み替えDNA実験計画についても学内委員会に提出し承認を得た。

The clinical research part of this study was approved by the internal ethics committee and the research plan was proposed and approved. Department of Defense Alzheimer's Disease Neuroimaging Initiative (DOD-ADNI): Observational study of past TBI, dementia, and PTSD diagnosis The application for obtaining the research is submitted, and the review of the examination is carried out. Analysis is carried out. Prepared analysis and screening visit, 369 names of が来院し, and このうちAPOE legacy type のinformation, 274 names of であった. The maintenance rate of APOE ε4 アレルの was 27.1% in the normal group (85 cases), 23% in the PTSD group (112 cases), and 32.5% in the TBI group (54 cases). There are 118 cases of PTSD and TBI in the combined group, which is 25%, and the maintenance rate of the TBI group is high. ε４アレルmaintains the cognitive function after the event and the impact of the disease, 274 complete cases of various cognitive function tests (MMSE, MOCA, ADAS-cog13, Logical memory, Boston naming test, カテゴリーfluency, timepiece drawing, timepiece modeling, トレイルメイキングテスト, RAVLT) clinical evaluation index (CDR-SB, GDS, N PI) There is a comparison between the ε4 holding group (n=72) and the ε4 non-maintaining group (n=202).さらにTBI Injury Effect を検するため、TBI Group (TBI Single Group とTBI とPTSD Merged Group) 124 people limited してε4 The comparison between the holding group (n=34) and the non-maintaining group (n=90) is the same as the line and the difference between the point and point difference. The animal control part of this study was approved by the Animal Control Project and was approved by the Animal Control Ethics Review Committee of the National Defense Medical University. The project of converting the deceased into an animal using DNA was proposed and approved by the internal committee of the school.

项目成果

Amyloid-Related Imaging Abnormalities in the DIAN-TU-001 Trial of Gantenerumab and Solanezumab: Lessons from a Trial in Dominantly Inherited Alzheimer Disease.

• DOI: 10.1002/ana.26511
• 发表时间: 2022-11
• 期刊: ANNALS OF NEUROLOGY
• 影响因子: 11.2
• 作者: Joseph-Mathurin, Nelly;Llibre-Guerra, Jorge J.;Li, Yan;McCullough, Austin A.;Hofmann, Carsten;Wojtowicz, Jakub;Park, Ethan;Wang, Guoqiao;Preboske, Gregory M.;Wang, Qing;Gordon, Brian A.;Chen, Charles D.;Flores, Shaney;Aggarwal, Neelum T.;Berman, Sarah B.;Bird, Thomas D.;Black, Sandra E.;Borowski, Bret;Brooks, William S.;Chhatwal, Jasmeer P.;Clarnette, Roger;Cruchaga, Carlos;Fagan, Anne M.;Farlow, Martin;Fox, Nick C.;Gauthier, Serge;Hassenstab, Jason;Hobbs, Diana A.;Holdridge, Karen C.;Honig, Lawrence S.;Hornbeck, Russ C.;Hsiung, Ging-Yuek R.;Jack, Clifford R.;Jimenez-Velazquez, Ivonne Z.;Jucker, Mathias;Klein, Gregory;Levin, Johannes;Mancini, Michele;Masellis, Mario;McKay, Nicole S.;Mummery, Catherine J.;Ringman, John M.;Shimada, Hiroyuki;Snider, B. Joy;Suzuki, Kazushi;Wallon, David;Xiong, Chengjie;Yaari, Roy;McDade, Eric;Perrin, Richard J.;Bateman, Randall J.;Salloway, Stephen P.;Benzinger, Tammie L. S.;Clifford, David B.
• 通讯作者: Clifford, David B.

Immune checkpoint inhibitor-related myositis and myocarditis with multiple myositis-specific/?associated antibodies

免疫检查点抑制剂相关性肌炎和多种肌炎特异性/相关抗体的心肌炎

• DOI: 10.1016/j.jns.2022.120528
• 发表时间: 2023
• 期刊: Journal of the Neurological Sciences
• 影响因子: 4.4
• 作者: Isa Megumi;Hongo Yu;Sakamoto Naohiro;Yamazaki Keishi;Takazaki Hiroshi;Asakuma Junichi;Ikewaki Katsunori;Suzuki Kazushi
• 通讯作者: Suzuki Kazushi

A case of recurrent headache and ophthalmoplegia with a contrast-enhanced lesion of the oculomotor nerve in the cavernous region: an atypical phenotype of recurrent painful ophthalmoplegic neuropathy

复发性头痛和眼肌麻痹伴海绵体区动眼神经对比增强病变一例：复发性疼痛性眼肌麻痹神经病的非典型表型

• DOI: 10.5692/clinicalneurol.cn-001691
• 发表时间: 2022
• 期刊: Rinsho Shinkeigaku
• 作者: 阪本 直広;本郷 悠;髙﨑 寛;海田 賢一;池脇 克則;鈴木 一詩
• 通讯作者: 鈴木 一詩

Pattern and implications of neurological examination findings in autosomal dominant Alzheimer disease.

常染色体显性阿尔茨海默病神经学检查结果的模式和意义。

• DOI: 10.1002/alz.12684
• 发表时间: 2023
• 期刊: Alzheimer's & dementia : the journal of the Alzheimer's Association
• 作者: Vöglein,Jonathan;Franzmeier,Nicolai;Morris,JohnC;Dieterich,Marianne;McDade,Eric;Simons,Mikael;Preische,Oliver;Hofmann,Anna;Hassenstab,Jason;Benzinger,TammieL;Fagan,Anne;Noble,JamesM;Berman,SarahB;Graff-Radford,NeillR;Ghett
• 通讯作者: Ghett

Avoid or Embrace? Practice Effects in Alzheimer's Disease Prevention Trials.

• DOI: 10.3389/fnagi.2022.883131
• 发表时间: 2022
• 期刊: Frontiers in aging neuroscience
• 影响因子: 4.8