engleski

Frontotemporal dementias: update on recent developments in molecular genetics and neuropathology. Arh Hig Rada Toksikol 2009 ; 60: 117-22.

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 behavioral 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, 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 toward an accurate diagnosis, and facilitate the development of diagnosis and therapy, when new diagnostic tests and therapeutics are becoming realized.

Frontotemporal lobar degeneration; Progranulin; motor neuron disease; mutation; TARDBP; TDP-43 protein

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