2022 Fiscal Year Final Research Report
Analysis of cerebral amyloid angiopathy in hereditary ATTR amyloidosis
| Project/Area Number |
21K15701
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52020:Neurology-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Keywords | アミロイドーシス / 遺伝性ATTRアミロイドーシス / 脳アミロイド血管症 |
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| Outline of Final Research Achievements |
Pathological analysis of autopsied brain tissues from patients with ATTRv amyloidois showed a correlation of CAA progression with disease duration even after LT. Mass spectrometry analysis demonstrated the proportions of variant TTR in the total TTR in CAA amyloid fibrils were extremely high regardless of liver transplantation (LT). In contrast, the proportions of variant TTR in the total TTR in amyloid fibrils of the heart vessels were high in patients who did not undergo LT and low in patients who underwent LT. These results show clear evidence that variant TTR derived from the choroid plexus was responsible for amyloid deposits in leptomeningeal vessels, regardless of LT.
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| Free Research Field |
アミロイドーシス
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、ATTRvアミロイドーシスにおける脳アミロイド血管症の病態に脈絡叢由来の変異型TTRが多大に影響し、また、肝臓由来のTTRはほとんど影響しないことを明らかにした。これまで本疾患の治療として、肝移植療法、四量体安定化剤、遺伝子サイレシング療法が開発されたが、これらの肝臓をターゲットとした治療では本疾患の脳アミロイド血管症は抑制できない可能性があり、脈絡叢をターゲットとした治療が必要であることを本研究で明らかにできた点で学術的、社会的意義がある。
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