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

• Published in: Journal of neurochemistry 2001-01, Vol.76 (1), p.87-96
• Main Authors: Campbell, Bruce C. V., McLean, Catriona A., Culvenor, Janetta G., Gai, Wei Ping, Blumbergs, Peter C., Jäkälä, Pekka, Beyreuther, Konrad, Masters, Colin L., Li, Qiao‐Xin
• Format: Article
• Language: English
• Subjects: a-Synuclein; Aged; alpha-Synuclein; Biological and medical sciences; Blotting, Western; Brain Chemistry; Cerebellum - chemistry; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; dementia with Lewy bodies; Electrophoresis, Polyacrylamide Gel; Frontal Lobe - chemistry; Humans; Lewy Body Disease - metabolism; Medical sciences; Middle Aged; Molecular Weight; multiple system atrophy; Multiple System Atrophy - etiology; Multiple System Atrophy - metabolism; Myelin Sheath - chemistry; Myelin Sheath - ultrastructure; Nerve Tissue Proteins - analysis; Nerve Tissue Proteins - metabolism; Neurology; Neurons - chemistry; Oligodendroglia - chemistry; Parkinson Disease - metabolism; Parkinson's disease; Pons - chemistry; Reference Values; Sodium Dodecyl Sulfate - chemistry; Solubility; Synucleins; α‐synuclein
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2001.00021.x

Intracellular inclusions containing α‐synuclein (αSN) are pathognomonic features of several neurodegenerative disorders. Inclusions occur in oligodendrocytes in multiple system atrophy (MSA) and in neurons in dementia with Lewy bodies (DLB) and Parkinson's disease (PD). In order to identify disease‐associated changes of αSN, this study compared the levels, solubility and molecular weight species of αSN in brain homogenates from MSA, DLB, PD and normal aged controls. In DLB and PD, substantial amounts of detergent‐soluble and detergent‐insoluble αSN were detected compared with controls in grey matter homogenate. Compared with controls, MSA cases had significantly higher levels of αSN in the detergent‐soluble fraction of brain samples from pons and white matter but detergent‐insoluble αSN was not detected. There was an inverse correlation between buffered saline‐soluble and detergent‐soluble levels of αSN in individual MSA cases suggesting a transition towards insolubility in disease. The differences in solubility of αSN between grey and white matter in disease may result from different processing of αSN in neurons compared with oligodendrocytes. Highly insoluble αSN is not involved in the pathogenesis of MSA. It is therefore possible that buffered saline‐soluble or detergent‐soluble forms of αSN are involved in the pathogenesis of other αSN‐related diseases.