Objective/Rationale:
Gait disturbances in PD are characteristic of advanced Parkinson’s disease (PD); they are extremely disabling to the patient and can frequently lead to patient falls, fractures and decreased quality of life. We believe that an area of the brain called the medullary reticular formation (located in the brainstem) may be implicated in gait disturbances in PD. In this project we will investigate how neuropathology in this brain region is related to clinical scores of gait disability in Parkinson’s disease.
Project Description:
In collaboration with the Arizona Parkinson’s Disease Consortium we will examine post-mortem tissue sections of medullary reticular formation from PD and ILBD (incidental Lewy body disease) patients with different clinical scores of postural and gait instability, and in age-matched control patients. We will determine whether there is a correlation between the degree of PD pathology in the medullary reticular formation and the level of gait disability. We will determine the level of PD pathology in tissue sections by assessing alpha-synuclein pathology (alpha-synuclein is a protein which is component of Lewy bodies and Lewy neurites- the pathological hallmarks of PD), neuronal number and inflammatory reaction. We will correlate alpha-synuclein pathology in the medullary reticular formation in each patient with the clinical scores of gait disturbances.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Gait disturbances in PD patients are less responsive to mainstay Symptoms & Side Effects therapies than PD motor symptoms. The underlying causes of gait disturbances in PD are a highly underexplored area and are not understood. Further work to elucidate the pathophysioloy of gait disturbances in PD that could ultimately lead to the treatment of these disabling symptoms would significantly impact PD patients.
Anticipated Outcome:
We will learn whether there is a correlation between the degree of PD pathology in the medullary reticular formation, and clinical scores of gait disturbances in PD. We anticipate that the data generated by these studies will be used toward more extensive analyses in the future.