Pathomechanistic analysis of animal model of cerebral amyloid angiopathy-related inflammation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07958
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Kanazawa University
• Principal Investigator: Sakai Kenji 金沢大学, 附属病院, 講師 (00572306)
• Co-Investigator(Kenkyū-buntansha): 濱口 毅 金沢大学, 医学系, 准教授 (70452109) ; 山田 正仁 金沢大学, 医学系, 協力研究員 (80191336)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 脳神経内科 / 神経病理 / 脳血管障害 / 炎症 / アミロイド

Outline of Final Research Achievements

We obtained cerebrospinal fluid (CSF) samples of 15 patients with cerebral amyloid angiopathy-related inflammation/vasculitis (CAA-ri). We have tried to establish experimental method of examination of anti-amyloid β protein (Aβ) antibodies in the CSF samples by enzyme-linked immunosorbent assay (ELISA). Then, we have bred mouse model of Alzheimer’s disease. APP knock-in mice model (APPNL-G-F/NL-G-F) demonstrated insufficient frequency of Aβ deposition on the blood vessels. We have bred another mouse model of Alzheimer’s disease (R1.40 mouse) which showed CAA in the brain.
Analysis of CSF samples from patients with CAA-ri revealed lower CSF levels of Aβ40 and Aβ42 in comparison to those in patients with post-treatment CAA-ri. Moreover, brain specimens of the pre-treatment CAA-ri showed higher frequency of partially Aβ deposited blood vessels than those of the post-treatment CAA-ri.

Free Research Field

脳神経内科学

Academic Significance and Societal Importance of the Research Achievements

脳アミロイドアンギオパチー（CAA）関連炎症はステロイドや免疫抑制薬の投与で改善が見込める病態であるが、疾患特異的な治療法は確立されていない。治療法開発のためには動物モデルの確立とそれを用いた病態の詳細な解明が重要である。現時点ではCAA関連炎症マウスモデルの確立には至っていないが、研究継続に必要なCAA関連炎症症例の脳脊髄液を収集できており、今後も研究を継続する。
CAA関連炎症の脳脊髄液や病理標本の解析研究で、脳脊髄液のAβ40やAβ42の測定がCAA関連炎症における診断や治療マーカーとなりうることを明らかにした。