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