The pre-mortem diagnosis of Alzheimer's disease (AD) relies on a combination of cognitive assessment scores, and increasingly draws from advances in brain scanning. At the molecular level, a reduction in soluble Aß combined with an increase in tau protein levels may to this day represent the most reliable biomarkers. While a number of palliative treatments are on the market, to date all attempts to delay progression of the disease have failed. It can be argued that sensitive biomarkers and disease intervention strategies are most likely to emerge from a detailed understanding of the molecular etiology underlying AD. The talk will present vignettes into current AD research activities at the Tanz Centre for Research in Neurodegenerative Diseases which build on this premise. It will provide an overview of recent advances in the understanding of genetic AD risk factors. Using the biology surrounding Aß release and its presumed receptor-mediated toxicity as an example, it will provide insights into the clinical and molecular complexity underlying AD and its emerging relationship to prion diseases. Finally, it will discuss challenges and promising trends for uncovering molecular mechanisms of the disease which may lead to differential diagnostics and disease intervention strategies.