A new alpha synuclein mutation

Fig 6

α-Synucleinopathy associated with G51D SNCA mutation: A link between Parkinson’s disease and multiple system atrophy?

Acta Neuropathologica February 2013 (epub)

Aoife P. Kiely, Yasmine T Asi, Eleanna Kara, Patricia Limousin, Helen Ling, Patrick Lewis,  Christos Proukakis,Niall Quinn, Andrew J. Lees, John Hardy, Tamas Revesz, Henry Houlden and Janice L. Holton

a-Synucleinopathies share the common feature of depositions of a-synuclein protein in cells of the brain. In Parkinson’s disease (PD) these deposits occur in neurons or their processes and are known as Lewy bodies or Lewy neurites respectively. While the hallmark feature of Multiple System Atrophy (MSA) is the localisation of a-synuclein within oligodendrocytes, which is known as glial cytoplasmic inclusions (GCIs).

Interestingly, although several mutations of the SNCA gene, which encodes the a-synuclein protein, have been found to cause PD, none have yet been identified in MSA.

This report describes the unusual clinical progression and neuropathological features in a family in which carriers of a G51D mutation of the SNCA gene develop young onset parkinsonism. The neuropathology observed in the deceased family member described here, is particularly fascinating as it shares both the cellular pathology of Parkinsonism such as the characteristic features of cell loss, a-synuclein accumulation within neurons and the distinctive GCIs of MSA. In addition a-synuclein inclusions in both cell types were abundant and widespread affecting both areas typically associated with PD and MSA and those which are generally less affected such as the striatum and both the superior and deep cortical layers. This pathology of combined cellular features of PD and MSA appears to be similar to cases reported which have A53T SNCA mutation and multiplication of the SNCA gene. This could suggest that, like in cases of over production of a-synuclein, cases with mutations in this region of the protein could have the ability to accumulate in and/or not be cleared from, greater numbers of cells and cell types. For this reason the data described in this paper provides us with interesting insight in the mechanisms which result in the distinct pathologies of both PD and MSA.

Contributed by Dr Aoife Kiely


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