The yeast Saccharomyces cerevisiae, a unicellular eukaryotic model, has enabled major breakthroughs in our understanding of a plethora of cellular and molecular processes. Today, a 're-invention' of its use in fundamental and applied research is paving the way for a better understanding of the mechanisms causing neurodegeneration. The increasing emergence of neurodegenerative disorders is becoming more and more problematic in our ageing society. Most prevalent is Alzheimer's disease (AD), affecting more than 35 million people worldwide (Abbott, Nature 475, S2-S4, 2011) and causing an enormous burden on a personal and communal level. The disease is characterized by two major pathological hallmarks: extracellular amyloid plaques consisting mainly of deposits of amyloid β (Aβ) peptides, and intracellular neurofibrillary tangles (NFTs), consisting mainly of aggregates of hyperphosphorylated tau protein. Despite the huge importance of thoroughly understanding the underlying molecular mechanisms of neurodegeneration, progress has been slow. However, multiple complementary research methods are proving their value, particularly with the work done with S. cerevisiae, which combines well-established, fast genetic and molecular techniques with the ability to faithfully capture key molecular aspects of neurodegeneration. In this review chapter, we focus on the considerable progress made using S. cerevisiae as a model system for Alzheimer's disease.

Over the past decade, the baker's yeast Saccharomyces cerevisiae has proven to be a useful model system to investigate fundamental questions concerning the pathogenic role of human proteins in neurodegenerative diseases such as Parkinson's disease (PD). These so-called humanized yeast models for PD initially focused on α-synuclein, which plays a key role in the etiology of PD. Upon expression of this human protein in the baker's yeast Saccharomyces cerevisiae, the events leading to aggregation and the molecular mechanisms that result in cellular toxicity are faithfully reproduced. More recently, a similar model to study the presumed pathobiology of the α-synuclein interaction partner synphilin-1 has been established. In this review we will discuss recent advances using these humanized yeast models, pointing to new roles for cell wall integrity signaling, Ca2+ homeostasis, mitophagy, and the cytoskeleton.

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