13 Aug Parkinson’s Disease: ApoA1 may be a Protection Marker
MedicalResearch.com: What are the main findings of the study?
Answer: Parkinson’s disease (PD) is an incurable neurodegenerative disease. Many neurons die, but the neurons that make dopamine (dopaminergic neurons) are particularly vulnerable. We think that the disease actually starts well before the time when people show clinical symptoms. We were therefore interested in finding proteins from the blood that correlated with better or worse dopaminergic neuron integrity. Since it’s hard to access the dopaminergic neurons directly, we looked at a tracer that labels the ends of the dopaminergic neurons in people who do not have Parkinson’s disease but are at high risk for developing it, and we also looked at the age at onset of PD in people who are already symptomatic. Screening just under 100 different proteins from the blood, we found that higher plasma levels of apolipoprotein A1 (ApoA1) were correlated with better tracer uptake in the people who did not yet have PD, and with older ages at onset in the people who already had PD. These data suggest that plasma ApoA1 may be a marker for PD risk, with higher levels being relatively protective.
MedicalResearch.com: Were any of the findings unexpected?
Answer: The fact that ApoA1 emerged from this unbiased screen (any of the proteins we tested could have been the one showing the best correlations) is interesting because ApoA1 is a protein we know a lot about. It’s actually one of the main components of high density lipoprotein (HDL) or “good” cholesterol.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Answer: I think the first step is just making sure we see this same signal in many, many people. In our paper, we showed that we see this relationship between high levels of plasma ApoA1 and older ages at PD onset in 152 PD patients from our clinical center at the University of Pennsylvania. We then showed that the same relationship existed in 187 PD patients from the University of Washington, using a different method for measuring ApoA1. The result for the tracer came from 134 people at risk for PD who are part of the Parkinson’s Associated Risk Study. While these are not small numbers, I would like to know that the same relationship holds in many more people from many clinical sites. If that is the case, then I hope we start thinking about (1) what the underlying biology behind the signal might be, and (2) whether we can protect dopaminergic neurons from dying by manipulating this pathway. The latter is particularly important because, as a clinician, I can offer my patients medications for their symptoms, but I cannot offer them much to slow down or stop the disease itself.
Qiang, J. K., Wong, Y. C., Siderowf, A., Hurtig, H. I., Xie, S. X., Lee, V. M.-Y., Trojanowski, J. Q., Yearout, D., B. Leverenz, J., Montine, T. J., Stern, M., Mendick, S., Jennings, D., Zabetian, C., Marek, K. and Chen-Plotkin, A. S. (2013), Plasma apolipoprotein A1 as a biomarker for Parkinson disease. Ann Neurol.. doi: 10.1002/ana.23872