Biochemistry of frontotemporal dementia

Masato Hasegawa

Department of Molecular Neurobiology, Tokyo Institute of Psychiatry

Frontotemporal dementia (FTD) is a clinical syndrome arising from the degeneration of the frontal and temporal lobes of the brain. Genetic analysis of familial FTD cases demonstrated that a proportion of FTD resulted from mutations in the tau gene on chromosome 17. So far, all FTD cases with tau gene mutations have shown tau pathology in the affected region of the brains, suggesting a close link between tau mutations and the filamentous tau inclusions. However, no tau pathology has been detected in about 60% of FTD cases. In the FTD cases without tau pathology, unique tau-negative, ubiquitin-positive inclusions have been reported and the presence of the inclusions is becoming increasingly recognized as the most common subtype of FTD. Identification of the ubiquitin-target protein in the inclusion bodies in FTD patients may play a key role in the elucidation of the pathogenesis of FTD and may establish a new proteinopathy.

Address correspondence to Dr. Masato Hasegawa, Department of Molecular Neurobiology, Tokyo Institute of Psychiatry (2-1-8, Kamikitazawa, Setagayaku, Tokyo 156-8585, Japan)