Mechanisms of disease in frontotemporal lobar degeneration: gain of function versus loss of function effects

Abstract

Frontotemporal lobar degeneration (FTLD) is clinically, pathologically and genetically heterogeneous. The prototypical clinical syndromes are behavioural variant frontotemporal dementia (bvFTD), a disorder of behaviour and executive impairments, progressive non-fluent aphasia (PNFA), a disorder of expressive language, and semantic dementia (SD), a disorder of conceptual knowledge [Neary et al 1998]. A proportion of patients with any of these syndromes of FTLD can develop the amyotrophic form of motor neurone disease (MND) [Neary et al 1990, Strong et al], further emphasising clinical heterogeneity within FTLD, and highlighting the long known association with, and suspected pathogenetic links between, FTLD and MND.