2022 Fiscal Year Final Research Report
mitochondrial dysfunction and neuroinflammation in early stage of dementia with Lewy bodies disease
| Project/Area Number |
20K07901
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52020:Neurology-related
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| Research Institution | National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders |
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Principal Investigator |
Terada Tatsuhiro 独立行政法人国立病院機構(静岡・てんかん神経医療センター臨床研究部), その他部局等, その他 (80550178)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | レビー小体型認知症 / PET / ミトコンドリア |
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| Outline of Final Research Achievements |
To examine the mitochondrial dysfunction and its relationship between dementia with Lewy body (DLB) pathology, we used novel PET tracer [18F]BCPP-EF which binds to mitochondrial complex 1. Nine DLB patients (CDR was 0.5 or 1) and controls underwent PET scans with [18F]BCPP-EF, [18F]FDG (glucose metabolism), and [11C]DPA713 (activated microglia) respectively. DLB patients showed reduced [18F]BCPP-EF bindings in the precuneus, posterior cingulate gyrus, and lateral occipital cortex, but not in the intra occipital cortex. [18F]FDG analysis revealed glucose hypometabolism more broadly including the intra occipital cortex. [11C]DPA713 bindings was significantly increased in the whole brain especially in the intra and lateral occipital cortex. Mitochondrial dysfunction is present even at the early stage of DLB, but not in the intra occipital area. The glucose hypometabolism in the intra occipital area was overlapped the brain area in which activated microglia was significantly increased.
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| Free Research Field |
神経内科学
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| Academic Significance and Societal Importance of the Research Achievements |
DLBは本邦で著しく増加しつつある三大認知症の一つであり、その病態解明と治療法の確立は重要な課題である。DLBの主要病理はαシヌクレイン沈着だが、その神経細胞死にはミトコンドリア機能障害が関わっている。生体脳におけるミトコンドリア障害とDLB病態との関連は未だ不明である。新規開発されたミトコンドリア電子伝達系酵素複合体1(MC-1)の活性を評価できる薬剤[18F]BCPP-EFを用いてミトコンドリア障害の分布・程度をPETで評価し、神経炎症、タウ、脳萎縮、認知機能との関連を検討することは、ミトコンドリア障害のDLB病態への関わりを明らかにし、早期診断、治療評価法の確立に寄与する可能性がある。
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