A novel 伪-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson's disease-type pathology

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• 作者：Petra Pasanen^a ; ^b ; Liisa Myllykangas^a ; ^c ; ^{liisa.myllykangas@helsinki.fi" class="auth_mail} ; Maija Siitonen^b ; Anna Raunio^c ; Seppo Kaakkola^d ; Jukka Lyytinen^d ; Pentti J. Tienari^d ; ^e ; Minna Pö ; yhö ; nen^a ; ^f ; ^g ; Anders Paetau^c
• 关键词：SNCA ; Genetics ; Neuropathology ; Parkinsonism ; A53E ; Synucleinopathy
• 刊名：Neurobiology of Aging
• 出版年：September 2014
• 年：2014
• 卷：35
• 期：9
• 页码：2180.e1-2180.e5
• 全文大小：1230 K

文摘

We describe the clinical, neuropathological, and genetic features of a Finnish patient with a novel 伪-synuclein (SNCA) mutation A53E. The patient was clinically diagnosed with atypical Parkinson's disease (PD) with age of onset at 36 years. In the neuropathological analysis performed at the age of 60 years, highly abundant SNCA pathology was observed throughout the brain and spinal cord showing features of multiple system atrophy and PD. Neuronal and glial (including oligodendroglial) SNCA inclusions and neurites were found to be particularly prominent in the putamen, caudatus, amygdala, temporal and insular cortices, gyrus cinguli, and hippocampus CA2-3 region. These areas as well as the substantia nigra and locus coeruleus showed neuronal loss and gliosis. We also found TDP-43 positive but mostly SNCA negative perinuclear inclusions in the dentate fascia of the hippocampus. The A53E mutation was found in 2 other relatives who had parkinsonism. Our results suggest that the novel SNCA A53E substitution is a causative mutation resulting clinically in parkinsonism and pathologically in severe multiple system atrophy- and PD-type phenotype.