Immunochemical analysis of vesicular monoamine transporter (VMAT2) proteinin Parkinson's disease

The vesicular monoamine transporter (VMAT2) has been suggested to be an exc ellent marker of presynaptic dopaminergic nerve terminals in the striatum o f Parkinson's disease patients based on its high level of expression and in sensitivity to drugs used to treat the disease. Previous in vivo imaging an d postmortem binding studies have detected a loss in striatal VMAT2 binding in Parkinson's diseased (PD) brain; however, these techniques have poor sp atial resolution and may suffer from nonspecific binding of some ligands. I n this study, we use novel polyclonal antibodies to distinct regions of hum an VMAT2 to quantify and localize the protein. Western blot analysis demons trated marked reductions in VMAT2 immunoreactivity in putamen, caudate, and nucleus accumbens of PD brain compared to control cases. Immunohistochemis try revealed VMAT2 immunoreactive fibers and puncta that were dense through out the striatum of control brains, but which were drastically reduced in p utamen of PD brains. In PD brains the caudate showed a significant degree o f sparing along the border of the lateral ventricle and the nucleus accumbe ns was relatively preserved. The distribution of VMAT2 in striatum and its loss in PD paralleled that of the dopamine transporter (DAT), a phenotypic marker of dopamine neurons. Thus, immunochemical analysis of VMAT2 protein provides novel and sensitive means for localizing and quantifying VMAT2 pro tein and nigrostriatal dopamine terminals in PD. Furthermore, the relative expression of VMAT2 compared to that of DAT may predict the differential vu lnerability of dopamine neurons in PD. (C) 1999 Academic Press.