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2016 Fiscal Year Final Research Report

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

Research Project

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Project/Area Number 26461733
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Psychiatric science
Research InstitutionUniversity 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

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Published: 2018-03-22  

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