Alpha-synuclein is a presynaptic protein that is implicated in the pathogenesis of various neurodegenerative diseases. Missense mutations in the alpha-synuclein gene are linked to familial cases of Parkinson's disease (PD), and it has further been shown that alpha-synuclein is a major constituent of the Lewy bodies in sporadic PD and dementia with Lewy body (DLB). The contribution of alpha-synuclein to the pathological changes in Alzheimer's disease (AD) has been currently a matter of scientific debate. Some reports hypothesized that alpha-synuclein may play a role in amyloid beta/A4 protein (Abeta) aggregation in senile plaques, whereas recent reports challenged this finding by showing a lack of alpha-synuclein-immunoreactivity in Abeta plaques. In this review, we report on recent findings on the physiological and pathological role of alpha-synuclein and try to elucidate its possible contribution to AD pathology.