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2019 Biomarkers Across Neurodegenerative Diseases Grant (BAND)

Examination of pS129-a-synuclein as a biomarker in brain-derived exosomes

Could a blood test increase the diagnostic accuracy of Parkinson’s disease and related diseases?

Gal Bitan, Ph.D.
University of California
Los Angeles, CA - United States


Parkinson’s disease shares diverse symptoms with a number of diseases called “parkinsonian disorders” such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and dementia with Lewy Bodies (DLB). This can make it more challenging to obtain an accurate diagnosis of Parkinson’s disease. Parkinson’s is characterized by specific brain changes, including the presence of Lewy bodies. Lewy bodies are chiefly comprised of alpha-synuclein, a protein that loses its normal shape and abnormally clumps together. Lewy body formation produces a series of damaging effects in the brain, as they begin to form inside nerve cells.  Lewy bodies are also a hallmark of DLB. 
Currently, the only way to diagnose Parkinson’s with certainty is by examining brain tissues of individuals who had Parkinson’s disease. Recently, scientists have developed a new method that provides a unique window into the biochemistry of the brain. This method uses tiny small pouch like structures called “exosomes” produced by most cells. These exosomes are released by cells in our body— including nerve cells in the brain— into the blood. The exosomes contain proteins and other materials such as DNA, RNA etc. of the original cells. Dr. Gal Bitan and colleagues will isolate the exosomes from the blood, determine the levels of the alpha synuclein protein and analyze them

Research Plan

In preliminary studies, Dr. Gal Bitan and colleagues have measured levels of the alpha-synuclein protein in exosomes that they have isolated from the blood of individuals with Parkinson’s disease, MSA and cognitively unimpaired individuals. The researchers have found that by measuring the alpha-synuclein levels in exosomes from two different brain cell types, they could distinguish between individuals with Parkinson’s and MSA with high accuracy.
As a next step, Dr. Bitan and colleagues will use the same strategy of isolating the exosomes from the blood, but instead of measuring all forms of alpha-synuclein they will only measure a special form of this protein. This special form of the protein known as pS129-alpha-synculein is thought to be associated with the progression of brain changes seen in different diseases. Dr. Bitan believes that pS129-alpha-synculein will provide an even higher diagnostic power than their earlier studies.


If successful, a blood test can be used as a biological marker to accurately distinguish between different forms of Parkinsonian disorders.

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