Development of the animal models and diagnostic methods of dementia based on the molecular and pathological analyses of conformational abnormality of aggregated proteins

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461733
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: University of Tsukuba
• Principal Investigator: ARAI Tetsuaki 筑波大学, 医学医療系, 教授 (90291145)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 認知症 / 蛋白質 / 病理 / 変性

Outline of Final Research Achievements

We analyzed pathological tau in cases with Alzheimer's disease, Pick's disease, corticobasal degeneration and progressive supranuclear palsy. We found that immunoblot analysis of trypsin-resistant tau showed the different band patterns of the fragments among these diseases, reflecting different conformations of tau molecular species. Protein sequence and mass spectrometric analyses revealed the carboxyl-terminal region of tau comprises the protease-resistant core units of the tau aggregates. These unique assembled tau cores may be used to classify and diagnose disease strains. Furthermore, to investigate the influence of a decline in progranulin on neurodegenerative diseases, brains of granulin mutation cases were analyzed. Results showed a neuronal and glial accumulation of tau andα-synuclein in addition to that of TDP-43. These results suggest that progranulin reduction might be the cause of multiple proteinopathies due to the accelerating accumulation of abnormal proteins.

Free Research Field

老年精神医学　神経病理学