[Neuropathology of frontotemporal dementia]

Frontotemporal dementia (FTD) is a clinical phenotype of dementia, characterized by complex of clinical symptoms, including disinhibition, character change, increased appetite, sexual misconduct and language problems. Frontotemporal lobar degeneration (FTLD) is a pathological classification of neurodegenerative disorder and its core consists of Pick's disease (PiD). Historically, PiD was morphologically subclassified into three types, but recent immunocytochemical investigations defined type I as PiD with Pick bodies (three repeat tauopathy), type II as corticobasal degeneration (CBD, four repeat tauopathy) and type III as FTLD with ubiquitinated inclusions (FTLD-U). The recent progress provided an evidence that the majority of FTLD-U represented primary TDP 43 proteionopathy. Three major clinical phenotypes of FTLD consist of FTD, semantic dementia (SD) and progressive non-fluent aphasia (PNFA). Clinical and pathological correlative studies demonstrated that majority of the background pathology of FTD is PiD with Pick bodies, that of SD is FTLD-U and that of PNFA is CBD, although there are too many exceptions. Although FTD is one of the major clinical manifestations of FTLD, the most frequent pathological background of FTD is Alzheimer disease (AD). The degenerative processes causing FTD symptoms include dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and argyrophilic grain disease. Moreover, vascular process such as Binswanger disease and inflammatory process such as neurosyphilis could also present with FTD symptoms. Since FTD requires special clinical care distinct from AD, clinical diagnosis of FTD is quite important. But for the fundamental treatment based on background pathological processes, surrogate biomarkers, including structural and functional neuroimages and findings of cerebrospinal fluid, blood and urine, should be pursued for future progress in FTD research.