The frontal and temporal lobes of the brain degenerate to cause severely debilitating disease in a group of disorders called frontotemporal dementias. These diseases are both clinically and pathologically heterogeneous and although genetic causes have been identified in some rare familial cases, the causes and pathogenesis of these diseases remain largely unknown. Nigel Cairns is interested in clarifying the pathological changes in the brains of these patients who come to autopsy and the mechanisms by which nerve cells die and cause dementia. His multidisciplinary approach uses histological, biochemical, and cell biological experiments to determine the role of candidate pathological proteins in frontotemporal dementias. These experiments will throw new light on the pathogenesis of this enigmatic group of diseases and generate novel avenues for therapeutic intervention.