Tau-Gliosis Interaction in Tauopathies using Pathological Imaging

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K15357
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Tohoku Medical and Pharmaceutical University (2022); Tohoku University (2018-2021)
• Principal Investigator: Harada Aiko (石木愛子) 東北医科薬科大学, 医学部, 助教 (30778634)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: アルツハイマー病 / タウ / グリオーシス / PET / 神経炎症

Outline of Final Research Achievements

An optimized MAO-B-selective PET tracer 18F-SMBT1, in which the tau binding of 18F-THK5351 was removed, was developed and the gliosis evaluation was switched to 18F-SMBT1. The tau PET tracer 18F-SNFT1 was not available for clinical trials during the period of this study. Therefore, 18F-SMBT1 and 11C-PiB PET were performed in this study. In healthy subjects, 18F-SMBT1 accumulated in the thalamus, striatum, and brainstem regions, and in those with mild cognitive impairment or Alzheimer's disease, in the frontal, temporal, parietal, and cingulate gyri. A follow-up study was conducted in one healthy subject, and 18F-SMBT1 SUVR was almost invariant in the whole brain.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病を初めとした認知症性疾患は未だに根本治療がなく、主に原因タンパク質をターゲットとした治療薬開発が盛んである。本研究により脳内の炎症と原因タンパク質との相互関係が明らかになれば、現在開発中の治療法をさらに補強する新規治療法の開発につながる可能性がある。本研究により脳内の加齢性変化が可視化され、また認知症性疾患では加齢性変化に加え異常な神経炎症が生じていることが明らかとなった。後続研究により経時的変化および原因タンパク質との相互関係が明らかになれば、治療ターゲットが変わる可能性もあり、大きく期待される。