Frontotemporal lobar degeneration - An update on clinical, pathological and genetic findings

Frontotemporal lobar degeneration is the second most common form of cortica l dementia in the presenium after Alzheimer's disease. Clinically, based on consensus guidelines, three distinct disease entities can be distinguished : frontotemporal dementia, semantic dementia and progressive nonfluent apha sia. Dementia of frontal type and motor neuron disease inclusion dementia a re the most frequent neuropathological subtypes of frontotemporal lobar deg eneration. By using immunohistochemistry, the latter is characterized by th e presence of filamentous ubiquitin-reactive but tau-negative inclusions in nerve cell bodies and neurites. In contrast, Pick's disease and familial f rontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) are both characterized by abundant filamentous nerve cell inclusions made u p of the microtubule-associated protein tau. The recent discovery of more t han 15 different mutations in the tau gene in FTDP-17 brought the tau prote in to the centre stage. These findings had a major impact on our understand ing of neurodegenerative disorders characterized by tau filamentous inclusi ons in neurones and/or glial cells which are grouped under the generic term of tauopathies. However, as exciting these new molecular insights are, it would be inappropriate to lump frontotemporal lobar degeneration as tauopat hies. Recent neuropathological and genetic data strongly suggest that there is more than one genetic background for frontotemporal lobar degeneration. Copyright (C) 2001 S. Karger AG,Basel.