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Alpha-synuclein, a main component of Lewy bodies in synucleinopathies and senile plaques in Alzheimer disease, is centrally involved in neurodegeneration. Three different isoforms (α-synuclein 112, 126, and 140) resulting from alternative splicing have been described so far. The present study explores α-synuclein 126 mRNA expression levels in the prefrontal cortex of six patients with dementia with Lewy bodies, eight patients with Lewy body variant of Alzheimer disease, eight patients with Alzheimer disease, and 10 controls. Relative α-synuclein 126 expression levels were determined by real-time polymerase chain reaction with competimer technology. Alpha-synuclein 126 mRNA expression was markedly decreased in the three dementias in comparison with controls, suggesting an important role of this α-synuclein isoform in the normal brain.