Etiological assessments of neurodegenerative dementias by in-vivo imaging of pathological protein aggregates in the brain

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H05324
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: Higuchi Makoto 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 脳機能イメージング研究部, 部長(定常) (10373359)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 認知症 / イメージング / 薬剤開発 / モデル動物

Outline of Final Research Achievements

The current study was aimed at visualizing all major hallmark pathologies of neurodegenerative dementias, consisting of fibrillary amyloid-beta, tau, alpha-synuclein, and TDP-43 protein aggregates, in the brains of living patients and animal models. Using original imaging agents for tau lesions, [11C]PBB3 and [18F]PM-PBB3, tau fibrils were found to accumulate in close association with clinical manifestations in Alzheimer’s disease, frontotemporal lobar degeneration, chronic traumatic encephalopathy, late-onset depression, and related disorders. The development of imaging probes for alpha-synuclein and TDP-43 pathologies made successful progress, yielding compounds that were immediately applicable to first-in-human PET studies. Notably, new imaging agents for alpha-synuclein deposits provided the first demonstration of in-vivo optical and PET imaging of disseminating alpha-synuclein fibrillization in rodent and non-human primate models.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

アミロイドとタウ病変の生体脳イメージングにより、アルツハイマー病における両者の相互作用が示され、治療戦略上有用な情報が得られた。また、前頭側頭葉変性症や慢性外傷性脳症、高齢発症うつ病では、アミロイドよりもタウの沈着が発症や臨床症状に関連することが判明し、タウイメージングが診断や病勢評価に役立つ指標をもたらしうる。αシヌクレインおよびTDP-43病変プローブも臨床評価を開始できる段階まで開発が進み、世界に先駆けてヒトで病変の画像化が実現する可能性が高い。これにより、神経変性型認知症の100%近くを網羅する生体病理検査が可能になり、早期診断や治療介入ポイント決定に役立つ精密検査の実現が見込まれる。