Pathways of Neurodegeneration Underlying Dementia

Neurodegenerative disorders (NDDs) and dementia are the greatest disease burdens of our time, carrying an enormous personal, societal and economic burden. Although, NDDs are often thought of as individual entities in their clinical presentation, there is increasing evidence of considerable overlap of their aetiology and pathogenesis. This has led to discovery of overlapping biological processes underlying disease mechanisms including protein misfolding, ER stress, cellular transport, mitochondrial dysfunction and inflammation. These biological processes ultimately result in neuronal death and attendant disease symptomology but pathogenesis of NDDs is orchestrated by an intimate interaction of both neuronal and non-neuronal cells. We are now moving into an era where we have new human cellular models, novel genetic manipulation tools and high throughput single cell analysis techniques that allow interrogation of this commonality and complexity married to an aspiration to develop novel therapeutic strategies to delay, slow or reverse neurodegeneration. This chapter provides a brief gestalt of these evolving ideas.