Frontotemporal dementias (FTD) are the second most common type of presenile dementias, considered to be clinically and pathologically different from Alzheimer's dementia (AD). FTD differs clinically from AD because memory loss is rarely an early symptom. Instead, FTD is usually denoted by behavioural and language difficulties, and may co-occur with motor neuron disease (MND). Frontotemporal lobar degeneration (FTLD) with ubiquitin-positive, tau-negative inclusions (FTLD-U) is the most common underlying pathology with and without MND. TAR DNA-binding protein 43 (TDP-43), encoded by the TARDBP gene, has been identified as the major pathological protein of FTLD-U with or without MND, demonstrating that abnormal TDP-43 alone is sufficient to cause neurodegeneration. FTLD is a genetically complex disorder. A proportion of cases of FTLD-U have various pathogenic mutations in the progranulin (GRN) gene. Other FTLD-U entities with TDP-43 proteinopathy include FTLD-U with valosin-containing protein (VCP) gene mutation and FTLD with MND linked to chromosome 9p. In contrast, chromosome 3-linked dementia, a FTLD-U with chromatic modifying protein 2B (CHMP2B) mutation, has TDP-43 negative inclusions. Thus, TDP-43 defines a novel class of neurodegenerative diseases called TDP-43 proteinopathies. These recent discoveries will contribute to an accurate diagnosis, and facilitate the development of diagnosis and therapy. Frontotemporalne demencije (FTD) druga su po učestalosti grupa presenilnih demencija, koja se kliničkim simptomima i patologijom razlikuje od Alzheimerove demencije (AD). FTD se razlikuje od AD budući da je gubitak memorije rijetko prvi simptom bolesti. Umjesto toga, FTD karakteriziraju smetnje u ponašanju i govoru, a mogu se javiti i simptomi bolesti motornog neurona (BMN). Frontotemporalna lobarna degeneracija (FTLD) s ubikvitin-pozitivnim, tau-negativnim inkluzijama (FTLD-U) najučestalija je patološka slika s BMN-om ili bez njega. Glavni patološki protein FTLD-U s BMN-om ili bez njega je protein 43 vezan s DNA (TDP-43), kodiran od gena TARDBP, čija prisutnost je već dovoljna za nastanak neurodegenerativnih promjena. Glede genetike, FTLD je kompleksna bolest. Dio bolesnika s patološkom slikom FTLD-U pokazuje različite patološke mutacije progranulin (GRN) gena. Ostali FTLD-U entiteti s TDP-43-proteinopatijama uključuju: FTLD-U proteinom vezanim s valozinom i FTLD s BMN-om vezanim uz kromosom 9p. Nasuprot tomu, demencija vezana na kromosom 3, FTLD-U s CHMP2B-mutacijom, sadržava TDP-43-negativne inkluzije. Stoga, TDP-43-protein definira novu grupu neurodegenerativnih bolesti koje nazivamo TDP-43-proteinopatije. Ova novija otkrića pridonijet će točnijoj dijagnozi i ubrzati razvoj dijagnostike i terapije.