Figure 2.

Frontotemporal lobar degeneration (FTLD) molecular classification. Four subtypes (FTLD-Tau, FTLD-TDP, FTLD-FUS, and FTLD-UPS) can be distinguished, based on what is known about the major components that make up the pathological deposits (Tau protein, TDP-43, FUS and unknown protein). FTLD-Tau and FTLD-TDP are more common than FTLD-FUS and FTLD-UPS. Tau deposits are made of either three-repeat (3R), four-repeat (4R) or all six (3/4R) brain isoforms of tau. Together, FTLD-TDP, FTLD-FUS, and FTLD-UPS make up FTLD-U, which is characterized by the presence of tau-negative, ubiquitin-positive inclusions. In some cases of FTLD-U, the ubiquitinated protein is unknown; they are classified as FTLD-UPS, to indicate that the inclusions can currently only be identified by markers of the ubiquitin-proteasome system. Abbreviations: PSP, progressive supranuclear palsy; CBD, corticobasal degeneration; MSTD, multiple system tauopathy with presenile dementia; AGD, argyrophilic grain disease; GGI, globular glial inclusion; NIFID, neuronal intermediate filament inclusion disease; BIBD, basophilic inclusion body disease; UPS, ubiquitin-proteasome system.