Construction of infrastructure for elucidation of pathogenesis and therapeutic development of ATTR-type cerebral amyloid angiopahty

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07959
• 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: Shinshu University
• Principal Investigator: Sekijima Yoshiki 信州大学, 学術研究院医学系, 教授 (60322715)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: アミロイド / トランスサイレチン / 遺伝性ATTRアミロイドーシス / 脳アミロイドアンギオパチー / PiB-PET

Outline of Final Research Achievements

We investigated the clinical characteristics, and distribution and progression pattern of ATTR-type CAA by using PiB-PET imaging.
We enrolled 31 ATTRv amyloidosis patients. Eight patients developed CNS symptoms due to CAA. Mean duration of illness from onset to CNS symptom onset was 17 years. Seven patients developed TFNEs, 2 developed multiple cerebellar hemorrhages, and 2 developed cognitive decline. The amount of PiB accumulation increased as a function of disease duration. Annual increase rate of SUVR in female was significantly greater as compared with that in male. SUVR was significantly increased at the follow-up PET analysis as compared with the first PET analysis. The 3D-SSP analysis demonstrated that CNS amyloid deposition started in the upper middle surface of cerebellar cortex around 10 years after onset, and then spread out into entire surface of cerebellum, Sylvian fissure, and anterior part of longitudinal fissure of cerebrum around 15 years after onset.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

遺伝性ATTRアミロイドーシスは末梢神経障害や心筋症を主症状とする疾患であるが，肝移植，TTR四量体安定化薬（タファミジス），核酸医薬（パチシラン）などの開発によりこれらが克服され，本症患者の予後が改善している．しかし，これらの症状は中枢神経のアミロイドーシスには無効なため，長期生存患者で脳アミロイドアンギオパチーアンギオパチーによる中枢神経症状が大きな問題となっている．
本研究により遺伝性ATTRアミロイドーシスの中枢神経症状の特徴が明らかになった．またPiB-PETが本症における脳アミロイド沈着の早期診断および治療効果判定に有用なバイオマーカーであることが明らかになった．