2021 Fiscal Year Final Research Report
Clarifying pathophysiology of Alzheimer's disease based on systemic chronic inflammation and neurovascular unit dysfunction
| Project/Area Number |
19K07916
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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 52010:General internal medicine-related
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| Research Institution | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
麻生 泰弘 大分大学, 医学部, 助教 (80555194)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | Neurovascular unit / 全身性慢性炎症 / 脳内アミロイド蓄積 / 脳糖代謝量 / 大脳白質病変 / PET / MRI / アルツハイマー病 |
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| Outline of Final Research Achievements |
We performed 11C-Pittsburgh compound-B (PiB)-PET, 18F-fluorodeoxyglucose-PET, and measurement of biomarkers in serum or cerebrospinal fluid (CSF). ① CSF adiponectin levels, which regulate inflammation, were associated with cortical glucose metabolism. ②CSF levels of matrix metalloproteinases (MMP)-2 and MMP-7 are associated with brain amyloid deposition and severity of white matter lesions, respectively, ③New biomarkers of neurovascular unit, such as protein tyrosine phosphatase receptor type B(PTPRB), gap junction protein alpha-5(GJA5), adenosine triphosphate-sensitive inward rectifier potassium channel-8(KCNJ8), and von Willebrand factor(vWF) were associated with cortical amyloid deposition. PTPRB and GJA5 levels inversely correlated with mean PiB uptake, whereas KCNJ8 and vWF levels positively correlated with mean PiB uptake. These results suggest that inflammation and blood brain barrier dysfunction might be associated with the pathophysiology of Alzheimer's disease.
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| Free Research Field |
認知症
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は，発症前段階における全身性慢性炎症とアルツハイマー病(AD)の病態との関連をアミロイドPET，FDG-PET，MRI等の先端画像データを用いて検討する点で独創的である．研究結果から血液あるいは脳脊髄液中の炎症およびneurovascular unit(NVU)障害マーカーは，脳内アミロイド蓄積，あるいは脳糖代謝と関連することが明らかとなった．従って，発症前からの慢性炎症およびNVU障害はAD病態の進行に関与する可能性があり，慢性炎症およびNVU障害を標的とした信頼性，再現性の高いAD診断マーカーや新規治療法の開発に繋がる．
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