List of abbreviations

Aβ, β-amyloid; AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; CBD, corticobasal degeneration; CHO, Chinese hamster ovary; CNS, central nervous system; ESE, exon-splicing enhancer; ESS, exon-splicing silencer; FTD, frontotemporal dementia; FTDP-17, frontotemporal dementia with parkinsonism linked to chromosome 17; FTLD, frontotemporal lobar degeneration; IHC, immunohistochemistry; MAP, microtubule-associated protein; MND, motor neuron disease; MT, microtubule; NFT, neurofibrillary tangle; PD, Parkinson's disease; PDC, parkinsonism-dementia complex; PHF, paired helical filament; PiD, Pick's disease; PSG, progressive subcortical gliosis; PSP, progressive supranuclear palsy; SF, straight filament; TG, transgenic; WT, wild-type.

Introduction

In 1892, Arnold Pick described a woman with lobar brain atrophy who presented clinically with presenile dementia and aphasia (Pick, 1892), and thus, the first description of what is now classified clinically as frontotemporal dementia (FTD) (Neary et al., 1998; McKhann et al., 2001). The clinical syndromes of FTD are associated with several neuropathological abnormalities (Lund and Manchester Groups, 1994; McKhann et al., 2001). A subset of these disorders is characterized by the intracellular accumulations of filamentous material composed of the microtubule-associated protein (MAP) tau. The term ‘tauopathies’ was coined to refer to this seemingly heterogeneous group of neurodegenerative disorders that includes Pick's disease (PiD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), neurofibrillary tangle dementia, and argyrophilic grain disease (see ‘Sporadic tauopathies’, Chapter 11). In FTD patients, there is a family history of a similar dementing illness in approximately 38 to 50% of patients (Knopman et al., 1990b; Stevens et al., 1998; Chow et al., 1999).