The solubility of alpha-synuclein in multiple system atrophy differs from that of dementia with Lewy bodies and Parkinson's disease

Intracellular inclusions containing alpha -synuclein (alpha SN) are pathogn omonic features of several neurodegenerative disorders. Inclusions occur in oligodendrocytes in multiple system atrophy (MSA) and in neurons in dement ia with Lewy bodies (DLB) and Parkinson's disease (PD). In order to identif y disease-associated changes of aSN, this study compared the levels, solubi lity and molecular weight species of aSN in brain homogenates from MSA, DLB , PD and normal aged controls. In DLB and PD, substantial amounts of deterg ent-soluble and detergent-insoluble alpha SN were detected compared with co ntrols in grey matter homogenate. Compared with controls, MSA cases had sig nificantly higher levels of alpha SN in the detergent-soluble fraction of b rain samples from pens and white matter but detergent-insoluble alpha SN wa s not detected. There was an inverse correlation between buffered saline-so luble and detergent-soluble levels of alpha SN in individual MSA cases sugg esting a transition towards insolubility in disease. The differences in sol ubility of alpha SN between grey and white matter in disease may result fro m different processing of alpha SN in neurons compared with oligodendrocyte s. Highly insoluble alpha SN is not involved in the pathogenesis of MSA. It is therefore possible that buffered saline-soluble or detergent-soluble fo rms of alpha SN are involved in the pathogenesis of other alpha SN-related diseases.