The Parkinson's puzzle: Developing an assay to identify components in protein structures to aid diagnosis, treatment

March 26, 2013, Pacific Northwest National Laboratory
Photomicrographs showing Lewy bodies and Lewy neurites in various magnifications in a Parkinson's disease patient. Top panels show a 60x magnification of the alpha synuclein intraneuronal inclusions aggregated to form Lewy bodies. The bottom panels are 20x magnification images that show strand-like Lewy neurites and rounded Lewy bodies of various sizes. Credit: Suraj Rajan,

As part of a new initiative to speed the search for changes in the body that can help predict, diagnose, or monitor Parkinson's disease, a research team led by Pacific Northwest National Laboratory recently received a grant from the National Institute of Neurological Disorders and Stroke (NINDS). Scientists from PNNL, University of Miami, Baylor College of Medicine, and Rush University have teamed to identify new components of the Lewy bodies that accumulate in the brain during Parkinson's, and then use ultra-sensitive methods to see if any of these proteins have leaked into cerebrospinal fluid or blood.

Parkinson's disease is a movement disorder that affects about 1 million people in the United States. Symptoms of the disease get worse over time, and include uncontrollable shaking, rigidity, slowed movements, and impaired balance.

"Lewy bodies are abnormal that form in the of Parkinson's disease patients," said PNNL biochemist Dr. Vladislav Petyuk, principal investigator of this 3-year, $900K project. "Their presence is one of the signature signs of the disease's progression. Unfortunately, right now, their presence can only be determined after a person has died, because it requires direct examination of under the microscope."

The team plans to develop a Lewy body assay based on biofluid protein measurements. They will use proteomics data obtained from brain tissue samples from 500 deceased individuals in studies conducted by Rush University. Differentially abundant proteins exclusively expressed in the brain tissue will be targeted for follow-up testing in easily obtained biofluids.

Detection of Lewy bodies in living humans could allow direct and accurate diagnostics of the disease's onset and progression. It would also act as a surrogate endpoint for assessing drug efficacy during clinical trials. The availability of a minimally invasive test capable of detecting Lewy bodies in living individuals would constitute a significant and welcome development for both clinical diagnostics and drug trials.

"The availability of brain tissue, cerebrospinal fluid, and blood from the same individuals allows us to directly explore the relationship between protein abundance profiles in brain tissue and biofluids," said Petyuk.

Aiding the team in this exploration will be an ultra-sensitive selected reaction monitoring approach developed by PNNL scientists Dr. Wei-Jun Qian and Dr. Tujin Shi of the Biological Sciences Division and in EMSL, a national user facility located at PNNL. They will also use other mass spectrometry capabilities developed at PNNL to reach even lower levels of quantitation. The information will be used to develop a biofluid-based statistical model that predicts the Lewy body load. They will validate the model by acquiring blood serum measurements for an independent Parkinson's disease case/control cohort based on subjects enrolled in another study at Rush.

"The main innovation of our research lies in our approach for testing our assumption that cerebrospinal fluid and blood bear the footprint of brain protein abundances, though at very low concentrations," said Petyuk. "If our hypothesis turns out to be true, especially for blood, this brain-biofluid protein correlation will open an avenue for developing biomarkers of other neurodegenerative disorders."

Explore further: Researchers identify Parkinson's disease link

Related Stories

Researchers identify Parkinson's disease link

March 19, 2013
(Medical Xpress)—Researchers at the Virginia Commonwealth University Parkinson's and Movement Disorders Center have found that mitochondrial quality and functional capacity play an important role in Parkinson's disease.

Colonoscopy or flexible sigmoidoscopy may be used to predict Parkinson's

May 15, 2012
Two studies by neurological researchers at Rush University Medical Center suggest that, in the future, colonic tissue obtained during either colonoscopy or flexible sigmoidoscopy may be used to predict who will develop Parkinson's ...

Biomarkers in cerebrospinal fluid can identify patients with Alzheimer's disease

October 22, 2012
Analysis of specific biomarkers in a cerebrospinal fluid sample can differentiate patients with Alzheimer's disease from those with other types of dementia. The method, which is being studied by researchers at Sahlgrenska ...

Seeds of destruction in Parkinson's disease: Spread of diseased proteins kills neurons

October 5, 2011
New research suggests that small "seed" amounts of diseased brain proteins can be taken up by healthy neurons and propagated within them to cause neurodegeneration. The research, published by Cell Press in the October 6 issue ...

Parkinson's protein causes disease spread in animal model, suggesting way disorder progresses over time in humans

April 17, 2012
(Medical Xpress) -- Penn researchers have shown that brain tissue from a Parkinson's disease mouse model , as well as synthetically produced disease protein fibrils, injected into young, symptom-free PD mice led to spreading ...

Recommended for you

Parkinson's disease 'jerking' side effect detected by algorithm

January 8, 2018
A mathematical algorithm that can reliably detect dyskinesia, the side effect from Parkinson's treatment that causes involuntary jerking movements and muscle spasms, could hold the key to improving treatment and for patients ...

New brainstem changes identified in Parkinson's disease

January 4, 2018
A pioneering study has found that patients with Parkinson's disease have more errors in the mitochondrial DNA within the brainstem, leading to increased cell death in that area.

Caffeine level in blood may help diagnose people with Parkinson's disease

January 3, 2018
Testing the level of caffeine in the blood may provide a simple way to aid the diagnosis of Parkinson's disease, according to a study published in the January 3, 2018, online issue of Neurology, the medical journal of the ...

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.

Robotic device improves balance and gait in Parkinson's disease patients

December 19, 2017
Some 50,000 people in the U.S. are diagnosed with Parkinson's disease (PD) every year. The American Institute of Neurology estimates there are one million people affected with this neurodegenerative disorder, with 60 years ...

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 ...


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.