Frontotemporal lobar degeneration (FTLD) is a group of neurodegenerative diseases that have in common the progressive involvement of the frontal and temporal lobes. They are characterized by progressive changes in behavior, cognitive dysfunction and language disorders. There are several clinical types: semantic dementia, non-fluent progressive primary aphasia, frontotemporal dementia (FTD) behavioral variant, FTD with amyotrophic lateral sclerosis (FTD-ALS).
Most FTLDs, whether sporadic or familial, are linked to the accumulation of one of the following three proteins in neurons or glia: Tau, TDP-43 and FUS.
The Tau protein accumulates in Pick's disease, or in cases with mutation of the MAPT gene. TDP-43 is found in semantic dementia and in cases with mutation of the genes encoding progranulin (PGRN) or C9ORF72. In the latter cases, which are the most common, FTD is often associated with ALS. The FUS protein is preferentially detected in cases with early clinical onset. It is difficult to predict clinically what is the type of FTLD. Definite diagnosis can only be reached by post mortem brain analysis.