Immunochemical analysis of dopamine transporter protein in Parkinson's disease

Gary W. Miller, Julie K. Staley, Craig J. Heilman, Jeffrey T. Ferez, Deborah C. Mash, David B. Rye, Allan I. Levey

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Abstract

The plasma membrane dopamine transporter (DAT) is considered to be a reliable marker of presynaptic dopaminergic terminal loss. Previous in vivo imaging and postmortem binding studies have detected a loss in striatal DAT binding in Parkinson's diseased (PD) brain; however, these techniques have poor spatial resolution and may suffer from nonspecific binding of some ligands. In this study, we use novel highly specific monoclonal antibodies to distinct epitopes of human DAT to quantify and localize the protein. Western blot analysis revealed marked reductions in DAT immunoreactivity in putamen, caudate, and nucleus accumbens of PD brain compared with control cases, and the reductions were significantly correlated to disease duration. Immunohistochemistry revealed DAT-immunoreactive fibers and puncta that were dense throughout the striatum of control brains but that were drastically reduced in putamen of PD brains. Caudate from PD brains showed a significant degree of sparing along the border of the ventricle, and the nucleus accumbens was relatively preserved. An unexpected finding was that discrete islands of DAT immunoreactivity were preserved within the matrix of PD putamen. Thus, immunological analysis of DAT protein provides novel and sensitive means for localizing and quantifying DAT protein in PD and other neurological disorders involving dopaminergic systems.

Original languageEnglish (US)
Pages (from-to)530-539
Number of pages10
JournalAnnals of Neurology
Volume41
Issue number4
DOIs
StatePublished - Apr 29 1997

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ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Miller, G. W., Staley, J. K., Heilman, C. J., Ferez, J. T., Mash, D. C., Rye, D. B., & Levey, A. I. (1997). Immunochemical analysis of dopamine transporter protein in Parkinson's disease. Annals of Neurology, 41(4), 530-539. https://doi.org/10.1002/ana.410410417