Cerebrospinal fluid from patients with multiple system atrophy promotes in vitro α-synuclein fibril formation

The aggregation of α-synuclein (αS) in the central nervous system (CNS) is the hallmark of multiple system atrophy (MSA) and Lewy body diseases including Parkinson's disease (PD) and dementia with Lewy bodies (DLB) (α-synucleinopathies). To test the hypothesis that patients with α-synucleinopathies have a CNS environment favorable for αS aggregation, we examined the influence of cerebrospinal fluid (CSF) from patients with MSA (n = 20), DLB (n = 8), and PD (n = 10) on in vitro αS fibril (fαS) formation at pH 7.5 and 37 °C using fluorescence spectroscopy with thioflavin S, compared with those with hereditary spinocerebellar ataxia (hSCA) (n = 16), and tension-type headache (n = 7). CSF from MSA patients (MSA-CSF) promoted fαS formation more strongly than PD-, hSCA-, or headache-CSF. By electron microscopic analyses, the width of fαS formed in MSA-CSF was significantly greater than others. MSA may have a CSF environment particularly favorable for fαS formation.

Research highlights▶ CSF from patients with MSA (MSA-CSF) promoted α-synuclein (αS) fibril formation. ▶ α-Synucleinopathies-CSF promoted αS aggregation compared to non-α-synucleinopathies. ▶ The widths of αS fibril formed in MSA-CSF were greater than those in PD- or DLB-CSF.