[Progressive nonfluent aphasia].

Progressive nonfluent aphasia (PNFA) is one of the three clinically defined phenotypes of pathologically determined frontotemporal lobar degeneration (FTLD); the other 2 phenotypes are semantic dementia (SD) and behavioral variant of frontotemporal dementia (bvFTD). FTLD is classified on the basis of the accumulated proteins-tau, TDP-43, and FUS. FTLD-TDP-43 is further subclassified into 4 types, including cases with progranulin mutation in type 3, on the basis of immunocytochemical and immunochemical properties. FTLD-tau is classified into the following 4 types: Pick's disease (accumulation of three-repeat tau); corticobasal degeneration (CBD, accumulation of CBD-type four-repeat tau); progressive supranuclear palsy (PSP, accumulation of PSP-type four-repeat tau); and frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17, mutation of the tau gene). Because the Cambridge group included CBD, PSP, and FTDP-17 in FTLD-tau and the Manchester group excluded these 3 disorders from FTLD-tau, different descriptions of the PNFA background pathology are present in the literature. Clinical and pathological correlations have been well established between SD and FTLD-TDP-43 type 3, similar to those observed between Yuasa-Mitsuyama-type amyotrophic lateral sclerosis with dementia (ALSD) and TDP-43 proteinopathy type 2. However, no such correlation has been established between PNFA and bvFTD; the pathological background of PNFA includes PSP, CBD, Pick's disease, FTDP-17, FTLD-TDP-43 type 3, and even Alzheimer disease (AD). Surrogate biomarkers including CSF tau, phosphorylated tau, and Aβ as well as carbon-11-labeled Pittsburgh compound-B ((11)C-PIB) positron emission tomography (PET) scans can be used to differentiate between AD and FTLD. Further clinical, radiological, and pathological studies (dynamic neuropathology) are necessary for elucidating PNFA and bvFTD, which will help in establishing clinical and pathological correlations between these conditions.