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Author Notes:

Correspondence: Dr Gearing, Center for Neurodegenerative Disease, Whitehead Research Building, 615 Michael Street, 5th floor, Atlanta, GA 30322. E-mail:mgearin@emory.edu

Acknowlegments: We thank L. Roback, R. Baul, and H. Yi for excellent technical assistance.

We are also deeply grateful to the family of the twins for donating the twins’ brains and for their ongoing interest and involvement in this work, and to the Brain and Tissue Bank for Developmental Disorders at the University of Maryland for providing tissues from additional dystonia cases.


Research Funding:

This work was supported by the Emory-Morehouse Alzheimer’s Disease Center (NIH AG10130, M.G., B.H.W.), National Institutes of Health (R01-AT00612-01, J.L.J.; N521328, AG13154, and N537167, D.C.W.), the Fauver Family Foundation, the Emory American Parkinson’s Disease Association Center of Excellence, the National Science Foundation (MCB-0110464, S.O.; IBN9983078, C.-A.G.), and the University Research Committee of Emory University and by a J. Worley Brown fellowship (V.P.) and an Ellison Foundation senior scientist grant (D.C.W.).

Aggregation of Actin and Cofilin in Identical Twins with Juvenile-Onset Dystonia

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Journal Title:

Annals of Neurology


Volume 52, Number 4


, Pages 465-465

Type of Work:

Article | Post-print: After Peer Review


The neuropathology of the primary dystonias is not well understood. We examined brains from identical twins with DYT1-negative, dopa-unresponsive dystonia. The twins exhibited mild developmental delays until age 12 years when they began developing rapidly progressive generalized dystonia. Genetic, metabolic, and imaging studies ruled out known causes of dystonia. Cognition was subnormal but stable until the last few years. Death occurred at ages 21 and 22 years. The brains were macroscopically unremarkable. Microscopic examination showed unusual glial fibrillary acidic protein–immunoreactive astrocytes in multiple regions and iron accumulation in pallidal and nigral neurons. However, the most striking findings were 1) eosinophilic, rod-like cytoplasmic inclusions in neocortical and thalamic neurons that were actin depolymerizing factor/cofilin-immunoreactive but only rarely actin-positive; and 2) abundant eosinophilic spherical structures in the striatum that were strongly actin- and actin depolymerizing factor/cofilin-positive. Electron microscopy suggested that these structures represent degenerating neurons and processes; the accumulating filaments had the same dimensions as actin microfilaments. To our knowledge, aggregation of actin has not been reported previously as the predominant feature in any neurodegenerative disease. Thus, our findings may shed light on a novel neuropathological change associated with dystonia that may represent a new degenerative mechanism involving actin, a ubiquitous constituent of the cytoskeletal system.

Copyright information:

© 2002 Wiley-Liss, Inc.

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