Objective/Rationale:
Many patients with Parkinson´s disease (PD) eventually develop dementia, a severe form of cognitive deterioration, and widespread neurodegenerative processes affecting the cerebral cortex. Pathological changes in the cortex affect not only neurons but also the microvasculature, which may lead to an upregulation of angiogenic and proinflammatory mediators that, in turn, aggravate the neurodegenerative process.
Project Description:
We will measure the levels of angiogenic and proinflammatory mediators in post-mortem samples from PD patients, affected or not by dementia, comparing them to both Alzheimer patients and neurologically healthy individuals. We will try to relate the expression of these markers to pathological features of cortical microvessels on brain sections. In addition, we will determine whether levels of angiogenic and proinflammatory mediators correlate with some important clinical variables (including the exposure to dopaminergic medications). All samples and clinical information will be provided by the Banner Sun Health Research Institute in Arizona.
Relevance to Diagnosis/Treatment of Parkinson’s Disease and Expected Outcome:
The results of this study will help define new biomarkers to monitor the progression of cognitive decline in PD and will inform the development of novel preventive therapies.
Final Outcome
When a harmful event, such as disease, affects human body, it responds by growing new blood vessels to support the affected area with more oxygen and nutrients. This process is called angiogenesis. In this project, we measured the levels of angiogenic cytokines -- chemicals that promote angiogenesis -- in samples of cerebrospinal fluid (CSF) from people with Parkinson's disease (PD) and from healthy people. We also measured the density of small blood vessels and the production of chemical signs (markers) of angiogenesis in samples of brain cortex -- the outermost layer of the brain -- from deceased people who had PD and those who lived without PD. Both studies included two groups of people with PD: people with severe cognitive decline (dementia) and people without dementia. We found that, regardless of having dementia, people with PD had more angiogenic cytokines in the CSF than people without PD. We also found more small blood vessels in the brains of people with Parkinson's and dementia compared with those of people with Parkinson's but without dementia and those of healthy people. These promising results call for further studies of angiogenesis in the brain cortex and of its possible role in the development of dementia in Parkinson's disease.
September 2014