title: Atypical multiple system atrophy is a new subtype of frontotemporal lobar degeneration: frontotemporal lobar degeneration associated with α-synuclein.
abstract: Multiple system atrophy (MSA) is a sporadic neurodegenerative disease clinically characterized by cerebellar signs, parkinsonism, and autonomic dysfunction. Pathologically, MSA is an α-synucleinopathy affecting striatonigral and olivopontocerebellar systems, while neocortical and limbic involvement is usually minimal. In this study, we describe four patients with atypical MSA with clinical features consistent with frontotemporal dementia (FTD), including two with corticobasal syndrome, one with progressive non-fluent aphasia, and one with behavioral variant FTD. None had autonomic dysfunction. All had frontotemporal atrophy and severe limbic α-synuclein neuronal pathology. The neuronal inclusions were heterogeneous, but included Pick body-like inclusions. The latter were strongly associated with neuronal loss in the hippocampus and amygdala. Unlike typical Pick bodies, the neuronal inclusions were positive on Gallyas silver stain and negative on tau immunohistochemistry. In comparison to 34 typical MSA cases, atypical MSA had significantly more neuronal inclusions in anteromedial temporal lobe and limbic structures. While uncommon, our findings suggest that MSA may present clinically and pathologically as a frontotemporal lobar degeneration (FTLD). We suggest that this may represent a novel subtype of FTLD associated with α-synuclein (FTLD-synuclein).
authors.affiliation: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
authors.forename: Naoya
authors.initials: N
authors.lastname: Aoki
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Boyer
authors.forename: Cheryl
authors.initials: C
authors.lastname: Lund
authors.forename: Wen-Lang
authors.initials: WL
authors.lastname: Lin
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Koga
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.forename: Myron
authors.initials: M
authors.lastname: Weiner
authors.forename: Anne
authors.initials: A
authors.lastname: Lipton
authors.forename: James M
authors.initials: JM
authors.lastname: Powers
authors.forename: Charles L
authors.initials: CL
authors.lastname: White
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D019578:Multiple System Atrophy / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins