Research study in Diagnosing PD

Study Points Toward Diagnostic Test for Parkinson’s

– Jan 20 2017 published in the December 5 online edition of JAMA Neurology,

Using a new technology, researchers were able to detect trace amounts of toxic alpha-synuclein protein in the cerebrospinal fluid of people with Parkinson’s disease (PD), but not in people without PD. Furthermore, the amount of the protein increased with severity of PD. The results, suggest that the technique could be developed as a test to diagnose and monitor Parkinson’s disease.

Today, doctors diagnose PD based on a person’s symptoms, including tremor and stiffness. But many PD symptoms can be subtle, especially early on in the disease. Additionally, many PD symptoms can overlap with those of other disorders, making early diagnosis difficult. There is an urgent need for a simple test or biomarker that can definitively diagnose PD. Scientists have looked at the alpha-synuclein protein as a possible biomarker since it’s known to clump in the brain cells of people with PD.

In earlier research, scientists led by Claudio Soto, Ph.D., at the University of Texas-Houston Medical School, began working on a solution. First, they invented a way of isolating extremely small amounts of misfolded alpha-synuclein proteins. Then, they used a process similar to the one police use to identify trace amounts of DNA — a method called PMCA in which they used the small proteins as templates or seeds to make copies. After many cycles of copying, they had an amount large enough to analyze in the laboratory.

For the new study, the researchers used PMCA to search for alpha-synuclein aggregates in samples of cerebrospinal fluid — the clear fluid that bathes the brain and spinal cord — which contains small amounts of this abnormal protein (larger amounts are found in the brain). They assessed fluid from 76 people with PD and 97 people who were either healthy or had other neurological disorders.

For the new study, the researchers used PMCA to search for alpha-synuclein aggregates in samples of cerebrospinal fluid — the clear fluid that bathes the brain and spinal cord — which contains small amounts of this abnormal protein (larger amounts are found in the brain). They assessed fluid from 76 people with PD and 97 people who were either healthy or had other neurological disorders.

Results

  • The protein amplification technique detected tiny amounts (picogram per milliliter) of misfolded alpha-synuclein in samples from people with PD.
  • The technique was highly accurate identifying who had PD and ruling out those who did not.
  • Increasing PD severity, which was evaluated using the Hoehn and Yahr scale, correlated with higher amounts of misfolded alpha-synuclein.

What Does It Mean?

The results suggest that detecting toxic forms of alpha-synuclein using this new method, PMCA, may be useful in distinguishing people who live with Parkinson’s disease from those without it or those affected by other neurological conditions.

The results are very encouraging. Surprisingly, prior research measuring alpha-synuclein levels in spinal fluids could not successfully distinguish between those with PD and those without PD (in fact, sometimes levels were lower in people with PD). One possible explanation is that the new method, PMCA, may identify people with a more toxic form of alpha-synuclein aggregates.

The authors propose expanding their research to see if the method can also detect toxic alpha-synuclein in blood or urine (less complicated than testing cerebrospinal fluid). In addition, more research is needed to find out whether PMCA could be used to monitor PD progression or identify those who may develop the disease.

This study joins several others in recent years that have investigated potential biomarkers for PD in cerebrospinal fluid. Some of these have looked at various forms of alpha-synuclein as well as arrays of other proteins and chemicals that can be identified. The limiting factor in many of these studies is to be able to measure very, very small numbers of potentially important molecules. While the question remains open as to whether any of these potential biomarkers will be predictive or correlate to PD, this study solves the problem of not having enough molecules through a novel amplification process. If the target – misfolded alpha-synuclein – is indeed indicative of Parkinson’s, then these investigators have a new and effective way to measure it.

References: Shahnawaz M, Tokuda T, Waragai M, et al. (2016). Development of a Biochemical Diagnosis of Parkinson Disease by Detection of α-Synuclein Misfolded Aggregates in Cerebrospinal Fluid. JAMA Neurology doi:10.1001/jamaneurol.2016.4547

Bartels T. (2016). Conformation-Specific Detection of α-Synuclein: The Search for a Biomarker in Parkinson Disease. JAMA Neurology doi:10.1001/jamaneurol.2016.4813

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