Alpha-synuclein in Lewy body disease and Alzheimer's disease

Alzheimer's disease (AD) and Lewy body disease (LBD) are the most common ca uses of dementia in the elderly population. Previous studies have shown tha t cognitive alterations in these disorders are associated with synaptic los s. Injury and loss of synapses might be associated with altered function of synaptic proteins. Among them, recent studies have shown that abnormal agg regation and accumulation of synaptic proteins, such as alpha-synuclein, mi ght be associated with plaque formation in AD and Lewy body formation in LE D. Further reinforcing the hypothesis that alpha-synuclein plays a major ro le in the pathogenesis of these disorders, recent work has shown that mutat ions that alter the conformation of this molecule are associated with famil ial forms of Parkinson's disease, The mechanisms by which altered function or aggregation of alpha-synuclein might lead to neurodegeneration are not c ompletely clear; however, new evidence points to a potential role for this molecule in synaptic damage and neurotoxicity via amyloid-like fibril forma tion and mitochondrial dysfunction. In this manuscript we review the data l inking alpha-synuclein to the pathogenesis of AD and LED.