Research Proposal

Parkinson disease (PD) is the result of a progressive loss of dopaminergic neurons in a specific brain region, the substantia nigra, pars compacta (SN).  Presently, a definitive diagnosis of PD can only be done post-mortem, as it is based on the detection of “Lewy bodies,” unusual  sub-cellular globular structures found in the remaining dopaminergic neurons in the SN. Our inability to make an early, definitive diagnosis  of PD is the source of considerable frustration.   In the living,  PD is identified by the symptoms  it produces, and these are only  apparent after significant damage to the brain has already occurred.  Treatment can only be started after the disease has been identified, so it also can begin only when considerable damage has been done.  The inability to  identify PD at an earlier stage has also hindered our  understanding of the early stages of the disease, and how, and why, the disease occurs.

Recently, the assumption that the pathology of PD involves only, or even primarily, the SN has come to be questioned, following the discovery that PD progresses through several stages, involving different brain regions and probably even neurons outside the  brain, prior to its affects on the SN.  If the death of dopaminergic neurons outside the brain  occurs during an early stage in PD, it seems plausible that the death of these peripheral neurons would perturb the dopamine levels in peripheral tissue.  If so, we hypothesize that a decrease in dopamine levels in peripheral  tissue could  be an early indicator of PD.  and might provide a method for early detection of the disease.   A good indicator of the rate of dopamine production by peripheral neurons is the dopamine levels found in saliva.  The saliva from healthy individuals is known to have high dopamine levels, and since saliva can be easily and painlessly obtained,  it is ideal for determining dopamine levels in peripheral tissue.  In out study, we will measure the dopamine levels in the saliva of people with PD and compare these to the dopamine levels of  people who are of similar age but who do not have PD.  If the results show that the dopamine levels of the subjects with PD are lower than those who do not have the disease, this will support our hypothesis. The next step will be to test a larger group, all of whom are above age 50, but show no signs of PD.  We will monitor  these subjects for the next five years.  If subjects who had low salivary dopamine levels at the time of testing later develop PD, we will have found a method for early detection of PD.perhaps before substantial damage to the neurons of the central nervous system has occurred.