Normal Dopaminergic Nigrostriatal Innervation in SPG3A Hereditary Spastic Paraplegia

Abstract

SPG3A/atlastin-1 gene mutations cause an autosomal dominant form of hereditary spastic paraplegia (SPG3A-HSP). We used positron emission tomography with [¹¹C]DTBZ to assess nigrostriatal dopaminergic integrity in two unrelated adults with SPG3A-HSP due to the common SPG3A/atlastin-1 mutation, R239C. Nigrostriatal dopaminergic terminal density was normal. A difference from the human pattern of neurodegeneration is a critical limitation of this Drosophila model of SPG3A-HSP. This major difference between human SPG3A/atlastin-1 mutations and the Drosophila atl ^l phenotype has several possible explanations.

Keywords:

• atlastin
• dopamine
• striatum
• dihydrotetrabenazine
• positron emission tomography

Acknowledgements

This study was supported by grants NS15655 and NS053917 for the National Institute of Neurologic Disease and Stroke. The authors thank the subjects for their participation.