Protein levels in spinal fluid correlate to posture and gait difficulty in Parkinson's

February 21, 2018, Rush University Medical Center
Protein levels in spinal fluid correlate to posture and gait difficulty in Parkinson's
Dr. Jennifer Goldman, lead author of the study and movement disorders neurologist at Rush University Medical Center. Credit: Rush University Medical Center

Levels of a protein found in the brain called alpha-synuclein (α-syn) are significantly lower than normal in cerebrospinal fluid collected in Parkinson's disease patients suffering from postural instability and gait difficulty, a study led by movement disorders experts at Rush University Medical Center has found. The results recently were published online in the journal Movement Disorders.

"This report is an important contribution in our efforts to understand and quantify Parkinson's biology to accelerate drug development," said Mark Frasier, PhD, an author on the study and the of research programs at the Michael J. Fox Foundation, which provided funding for the study.

A mysteriously harmful presence

Alpha-synuclein's function in the brain is currently unknown but of great interest to Parkinson's researchers because it is a major constituent of Lewy bodies - the protein clumps that are the pathological hallmark of Parkinson's disease.

The illness gradually destroys neurons that produce the chemical dopamine, which conveys nerve signals, in turn causing the tremors and difficulty moving that are a common symptom of Parkinson's disease. The prevailing wisdom has been that these neurons may die from a toxic reaction to alpha-synuclein deposits.

However, Parkinson's disease has been linked to some gene variants that affect how the immune system works, leading to an alternative theory that alpha-synuclein causes Parkinson's disease by triggering the immune system to attack the brain.

In addition to its presence in the brain, alpha-synuclein can be found in peripheral tissues and body fluids. The Movement Disorders study, called BioFIND, is the first to try to differentiate the biomarkers of neurodegeneration in Parkinson's disease patients based on fluids collected from spinal fluid, blood and saliva.

The cross-sectional, observational study collected data and body fluid samples from 120 people with moderately advanced Parkinson's disease and 100 control volunteers across eight academic sites in the U.S. at two points over two weeks.

Dr. Jennifer G. Goldman, a neurologist at Rush University Medical Center and the study lead author, has profiled the Parkinson's-associated protein levels in these biofluids and their relationships to clinical features of the disease. The study found that levels of alpha-synuclein were lower in cerebrospinal fluid from Parkinson's patients with certain motor function impairments - specifically in those who had more problems with balance and walking compared to those with more tremor.

In addition, levels of beta-amyloid, known for its association with Alzheimer's disease, were lower in those with Parkinson's and related to worse scores on a memory recall in Parkinson's as measured on a rest of thinking and memory given to study participants.

The study also showed that alpha-synuclein levels in plasma and saliva did not differ between people with Parkinson's and control volunteers, and alpha-synuclein did not significantly correlate among other biological fluids.

Findings can help guide selection for clinical trials

"These are important insights for the ongoing pursuit of accessible biomarker tests to diagnose and track the disease," said Goldman. "For example, people with Parkinson's and lower beta-amyloid may be more likely to develop memory problems and therefore would benefit more from a cognitive therapy," said Goldman. "Enrolling this population in trials can help us see a treatment effect more clearly than testing the therapy on people who will not have this symptom."

Future studies may further explore biomarkers

Next steps include validation of these findings in the Parkinson's Progression Markers Initiative (PPMI), a biomarkers study sponsored by the Michael J. Fox Foundation that is following more than 1,500 people with Parkinson's or risk factors and control volunteers over at least five years. Additionally, trials ongoing or launching in the near future could use alpha-synuclein or beta-amyloid levels as exploratory biomarkers in motor symptom or cognition drug trials, respectively.

Parkinson's disease is the second most common age-related neurodegenerative disorder after Alzheimer's disease, affecting an estimated 7 million to 10 million people worldwide.

Many of the affected neurons signal via the neurotransmitter dopamine; therefore, traditional therapy continues to rely on dopamine replacement therapy. This approach alleviates symptoms, but does not halt disease progression. Currently, there is no cure for Parkinson's .

Explore further: Calcium may play a role in the development of Parkinson's disease

Related Stories

Calcium may play a role in the development of Parkinson's disease

February 19, 2018
Researchers have found that excess levels of calcium in brain cells may lead to the formation of toxic clusters that are the hallmark of Parkinson's disease.

Drug discovery: Alzheimer's and Parkinson's spurred by same enzyme

July 3, 2017
Alzheimer's disease and Parkinson's disease are not the same. They affect different regions of the brain and have distinct genetic and environmental risk factors.

Tug of war between Parkinson's protein and growth factor

September 18, 2017
Alpha-synuclein, a sticky and sometimes toxic protein involved in Parkinson's disease (PD), blocks signals from an important brain growth factor, Emory researchers have discovered.

New findings point to potential therapy for Parkinson's Disease

December 19, 2017
A new study, published in Proceedings of the National Academy of Sciences (PNAS), sheds light on a mechanism underlying Parkinson's disease and suggests that Tacrolimus—an existing drug that targets the toxic protein interaction ...

Researchers shed light on why exercise slows progression of Parkinson's disease

December 22, 2017
While vigorous exercise on a treadmill has been shown to slow the progression of Parkinson's disease in patients, the molecular reasons behind it have remained a mystery.

A new insight into Parkinson's disease protein

July 28, 2017
Abnormal clumps of certain proteins in the brain are a prominent feature of Parkinson's and other neurodegenerative diseases, but the role those same proteins might play in the normal brain has been unknown.

Recommended for you

New transgenic model of Parkinson's illuminates disease biology

October 11, 2018
Parkinson's disease (PD) is a neurodegenerative disorder that presents clinically with abnormal movement and tremors at rest. In the brain, PD is marked by the accumulation of the protein, α-synuclein (αS), into clumps ...

Early Parkinson's patients waiting too long to seek medical evaluation

September 27, 2018
The time between diagnosis and the institution of symptomatic treatment is critical in the effort to find a cure for Parkinson's Disease (PD). A paper published in Nature Partner Journal: Parkinson's Disease notes too many ...

Molecule capable of halting and reverting neurodegeneration caused by Parkinson's disease identified

September 25, 2018
The small SynuClean-D molecule interrupts the formation of the alpha-synuclein amyloid fibres responsible for the onset of Parkinson's disease, and reverts the neurodegeneration caused by the disease. The study, headed by ...

Genomic dark matter activity connects Parkinson's and psychiatric diseases

September 20, 2018
Dopamine neurons are located in the midbrain, but their tendril-like axons can branch far into the higher cortical areas, influencing how we move and how we feel. New genetic evidence has revealed that these specialized cells ...

Gene therapy shown to remove core component of Parkinson's disease

September 14, 2018
An international team led by Rush researcher Jeffrey Kordower, Ph.D., has moved a step closer to developing a treatment to clear brain cells of a protein that is an integral cause of Parkinson's disease. The team published ...

ADHD may increase risk of Parkinson's disease and similar disorders

September 12, 2018
While about 11 percent of children (4-17 years old) nationwide have been diagnosed with attention-deficit hyperactivity disorder (ADHD), the long-term health effects of having ADHD and of common ADHD medications remains understudied. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.