This study will identify abnormalities of a protein called alpha synuclein that is found in
the brain of patients with Parkinson's disease and related disorders to see if it can serve
as a disease marker. There is currently no treatment that will cure or delay progression of
Parkinson's disease. Thus, there is a need to find disease markers that can help diagnosis
the disease, follow its progression, and monitor the effects of treatment. This study will
examine and compare alpha synuclein from blood and cerebrospinal fluid (the fluid that
bathes the brain and spinal cord) of patients with Parkinson's disease, patients with
variants of the disease, and healthy normal volunteers to determine differences in the
protein that might serve as a disease marker.
Patients with neurodegenerative disorders such as Parkinson's disease and Parkinson plus
disorders (other diseases that are variants of Parkinson's disease) and healthy volunteers
between 18 and 80 years of age may be eligible for this study. Candidates are screened with
a medical history, physical examination, neurological evaluation, and blood tests. A brain
MRI (magnetic resonance imaging) scan is done if needed for diagnosis.
All participants have a blood sample drawn and a lumbar puncture (spinal tap). For the
lumbar puncture, a local anesthetic is given and a needle is inserted in the space between
the bones in the lower back where the cerebrospinal fluid circulates below the spinal cord.
A small amount of fluid is collected through the needle. The fluid is analyzed for specific
proteins and chemicals that are leaked from the brain in various disease states and that
cannot be measured in blood.
Participation of healthy volunteers is completed after the blood draw and lumbar puncture.
Patients with Parkinson's and related diseases return to the clinic once a year for 2 years
for a repeat blood draw and lumbar puncture to follow changes in the alpha synuclein protein
and to monitor disease progression. Patients with specific proteins of interest may also be
asked to come for a repeat lumbar puncture 6 months after the first procedure.
OBJECTIVE: Parkinson's disease (PD) is a progressive neurodegenerative disorder of unknown
etiology in which several underlying pathophysiological mechanisms including proteasomal
degradation, mitochondrial dysfunction, inflammation, oxidative stress, and excitotoxicity
may contribute to cell death. No treatment is known to cure or delay progression of PD, thus
there is a need to investigate measurable biologic markers for the purpose of diagnosis,
monitoring disease progression and effect of treatment. This study will focus on alpha
synuclein and its metabolic pathways as a potential biomarker, to assist in evaluation of
pathogenesis and future diagnostic and therapeutic options.
STUDY POPULATION: In this pilot study we plan to include 30 patients with Parkinson's
disease (PD), 30 patients with Parkinson plus disorders, and 30 control patients without
neurologic disease or autoimmune disorders.
DESIGN: Samples of serum, plasma and cerebrospinal fluid (CSF) will be collected from all
patients for analysis at the beginning of the study. The assay will be performed for various
proteins including cytokines primarily related to the alpha synuclein (AS) pathway. A repeat
CSF, plasma and serum analysis will be performed in patients with PD, and Parkinson plus
disorders at the end of one and two years to follow changes of protein expression profiles
with disease progression.
ASSESSMENT OF RISKS AND BENEFITS: This study will carry the risk associated with
venepuncture and lumbar puncture.
OUTCOME ESTIMATE AND POTENTIAL MEANING FOR THE FIELD: The primary outcome measure is to
correlate the changes of alpha synuclein phosphorylation in CSF, plasma and serum with
changes in UPDRS motor score in patients with PD over the period of 2 years, compared to
controls. The secondary aim of the study is to compare the protein expression profiles
between different synucleinopathies including PD, Multiple System Atrophy (MSA) and Dementia
with Lewy Bodies (DLB) with time. There are currently no validated surrogate disease markers
in PD or other related neurodegenerative disorders. Our work would hopefully help understand
pathophysiologic mechanisms in patients with PD, monitor disease progression using specific
biologic markers, and in future development of targeted therapies.
Patients between ages 18 to 80 years who are able to give informed consent.
Before any study related procedure is undertaken, the subject or his representative must
sign a consent form.
In those individuals with dementia, a legal guardian will need to sign the consent form
prior to any procedure.
Medical disorders such as lupus, diabetes, serious heart and kidney disease, thyroid
dysfunction and any chronic medical illness with the exception of hypertension and
Patients with any history of bleeding diatheses or abnormal platelets or PT/PTT. Patients
using anticoagulants and other drugs which can alter PT/PTT.
Patients with evidence of elevated intracranial pressure based on the imaging studies.