"The incidence and prevalence of dementia is rising as the world-wide population ages. Determining biomarkers for the early detection of underlying biology that will predict dementia progression reliably or, the monitoring of biological processes once present to track progression and treatment is necessary. Furthermore, these biomarkers will aid in the differentiation of dementia from normal ageing and between its subtypes, and in the development of sensitive and specific diagnostic and treatment methods. The current study will be the first to assess a new protein-aggregating biomarker of dementia, TAR-DNA-binding-protein-43 (TDP-43), in a population-based sample. TDP-43 was implicated in the biology of dementia in 2006 however its relevance to the population is unknown. This study will assess the significance of TDP-43 in relation to dementia in a population sample of older people who have undergone brain donation. The sample (n=350) is from the European Clinicopathological Studies in Europe (EClipSE). Each participant has been tracked longitudinally for up to twenty years (dependent on date of death), with clinical (e.g., dementia and other diagnoses such as diabetes, cognition and psychological symptomatology) data available. The three study objectives are: • The determination of the prevalence of pathological TDP-43 expression in a population-based sample of older people as a whole and relative to dementia status. • The determination of the relationships between pathological TDP-43 expression and other neuropathological markers of dementia as well as longitudinal cognition and psychological symptomatology. • The development of clinical criteria which are sensitive and specific to the presence of pathological TDP-43 expression during life. These investigations will have significant implications for the diagnosis, management and treatment of dementia syndromes, with the aim of decreasing the social and economic costs of dementia."