Published online by Cambridge University Press: 04 August 2010
A variety of sporadic and familial neurodegenerative disorders, characterized clinically by dementia and/or motor dysfunction, demonstrate intracellular accumulations of filamentous material composed of the microtubule-associated protein (MAP) tau (See chapters 29, ‘Neuropathology of Alzheimer's disease’, 34, ‘Pick's and other frontotemporal dementias’, 44, ‘Progressive supranuclear palsy’, and 45, ‘Corticobasal degeneration’). The term ‘tauopathies’ was coined to refer to this seemingly heterogeneous group of neurodegenerative disorders with filamentous tau deposits as their predominant histopathological feature. The progressive accumulation of filamentous tau inclusions in the absence of other disease-specific neuropathological abnormalities provided circumstantial evidence implicating tau dysfunction in disease onset and/or progression. However, the discovery of pathogenic tau mutations in a heterogeneous group of disorders termed frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) provided unequivocal confirmation of the central role of tau abnormalities in the etiology of neurodegenerative disorders (Foster et al., 1997; Poorkaj et al., 1998; Hutton et al., 1998; Spillantini et al., 1998c). This seminal finding has opened novel areas of investigation into the pathophysiologic mechanisms of tau dysfunction and the relationship of tau abnormalities to brain degeneration.
Familial frontotemporal dementia
In 1892, Arnold Pick described a woman with lobar brain atrophy, who presented clinically with presenile dementia and aphasia (Pick, 1892). Thus, this was the first description of what is now classified clinically as frontotemporal dementia (FTD) (McKhann et al., 2001).