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Acta Neuropathologica

, Volume 130, Issue 1, pp 93–105 | Cite as

Atypical multiple system atrophy is a new subtype of frontotemporal lobar degeneration: frontotemporal lobar degeneration associated with α-synuclein

  • Naoya Aoki
  • Philip J. Boyer
  • Cheryl Lund
  • Wen-Lang Lin
  • Shunsuke Koga
  • Owen A. Ross
  • Myron Weiner
  • Anne Lipton
  • James M. Powers
  • Charles L. WhiteIII
  • Dennis W. DicksonEmail author
Original Paper

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).

Keywords

Multiple system atrophy Frontotemporal lobar degeneration Neuropathology Pick body-like inclusions α-Synuclein 

Notes

Acknowledgments

We are grateful to all patients, family members, and caregivers who agreed to brain donation; without their donation these studies would have been impossible. We also acknowledge expert technical assistance of Linda Rousseau and Virginia Phillips for histology and Monica Castanedes-Casey for immunohistochemistry. This research was supported in part by a research grant from the Uehara Memorial Foundation, as well as NIH P50 NS072187, P50 AG16574 and P30 AG12300, as well as the CurePSP: Foundation for PSP|CBD and Related Disorders, The Mangurian Foundation, and The Robert E Jacoby Professorship in Alzheimer’s Disease Research.

Supplementary material

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Naoya Aoki
    • 1
  • Philip J. Boyer
    • 2
  • Cheryl Lund
    • 3
  • Wen-Lang Lin
    • 1
  • Shunsuke Koga
    • 1
  • Owen A. Ross
    • 1
  • Myron Weiner
    • 4
  • Anne Lipton
    • 4
  • James M. Powers
    • 5
  • Charles L. WhiteIII
    • 6
  • Dennis W. Dickson
    • 1
    Email author
  1. 1.Department of NeuroscienceMayo ClinicJacksonvilleUSA
  2. 2.Department of PathologyUniversity of ColoradoDenverUSA
  3. 3.Department of AnesthesiologyVenice Regional HospitalVeniceUSA
  4. 4.Department of Psychiatry and NeurologyUniversity of Texas Southwestern Medical CenterDallasUSA
  5. 5.Department of PathologyUniversity of Rochester Medical CenterRochesterUSA
  6. 6.Department of PathologyUniversity of Texas Southwestern Medical CenterDallasUSA

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