title: Cerebrospinal fluid from patients with multiple system atrophy promotes in vitro α-synuclein fibril formation.
abstract: 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.
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Hirohata
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ono
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Morinaga
authors.forename: Tokuhei
authors.initials: T
authors.lastname: Ikeda
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000134:cerebrospinal fluid* / Q000473:pathology; D009410:Nerve Degeneration / Q000134:cerebrospinal fluid* / Q000473:pathology; D009454:Neurofibrils / Q000378:metabolism* / Q000473:pathology; D020754:Spinocerebellar Ataxias / Q000134:cerebrospinal fluid / Q000473:pathology; D018781:Tension-Type Headache / Q000134:cerebrospinal fluid / Q000473:pathology; D051844:alpha-Synuclein / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein