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Updated: Feb 2, 2026

Detection of Disease-associated α-synuclein by Enhanced ELISA in the Brain of Transgenic Mice Overexpressing Human A53T Mutated α-synuclein
Published on: May 30, 2015
Parkinsonism due to A53E α-synuclein gene mutation: Clinical, genetic, epigenetic, and biochemical features
Marina Picillo1,2,3, Karlo J Lizarraga2,3, Erik L Friesen4
1Center for Neurodegenerative Diseases (CEMAND), Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
Background:
SNCA mutations cause autosomal dominant parkinsonism and inform our understanding of the molecular underpinnings of synucleinopathies. The most recently identified mutation, p.Ala53Glu (A53E), has only been observed in Finland. The objectives of this study were to examine clinical, genetic, epigenetic, and biochemical features of the first family outside Finland with A53E.
Methods:
We examined a Canadian family with parkinsonism because of A53E using haplotype and DNA methylation analyses. We assessed aggregation properties of A53E α-synuclein in vitro.
Results:
Family members with parkinsonism shared a common haplotype distinct from Finnish patients with A53E. Increased acceleration of DNA methylation age was accompanied by earlier age at onset in the family members. We demonstrate that A53E α-synuclein has a propensity to form oligomers and phosphorylation promotes fibrillation.
Conclusions:
A53E as a cause of parkinsonism is not restricted to Finnish individuals. DNA methylation may contribute to disease age at onset. A53E enriches α-synuclein oligomers and fibrils dependent on the phosphorylation state. © 2018 International Parkinson and Movement Disorder Society.
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