A new biological test may revolutionize diagnosis of Parkinson’s disease and dementia with Lewy bodies

A hallmark brain change associated with both Parkinson’s disease and dementia with Lewy bodies (DLB) is the formation of Lewy bodies in brain cells; Lewy bodies are dense collections of a misfolded protein called alpha-synuclein, or a-syn. In the past, the only way to see these changes has been by looking directly at the brain after death for these telltale signs, which are visible under a microscope.

However, recently published data has shown that a new test of cerebrospinal fluid (CSF, the fluid that surrounds and protects the brain and spinal cord) can detect the presence of Lewy bodies with high accuracy in people with Parkinson’s disease. Based on these data, the test can correctly determine who has Parkinson’s disease with a simple lumbar puncture—or “spinal tap”—and may help researchers identify people with Parkinson’s disease potentially many years before the appearance of movement dysfunction or cognitive changes. This advance is making headlines as it has the potential to propel research advances not just for Parkinson’s disease but also other Lewy body disorders such as DLB.

As with any research advance, though, there are many unknowns that need to be addressed by further research. One of the most important questions is how well the test can predict who will develop Lewy body disorders. The vast majority of the data gathered so far has been collected once in individuals with Parkinson’s disease, rather than by following individuals over time and collecting the data at multiple time points. For this reason, we cannot yet say exactly what the test means in terms of risk for later disease when it is positive in people who do not yet have symptoms. It is likely that some will develop Parkinson’s disease, some will develop DLB, and some may never develop any symptoms.

How does the test work?

The new test is called an alpha-synuclein seeding amplification assay (a-syn-SAA). Briefly, a small amount of the CSF is collected during a spinal tap. Then the CSF is added to a test tube containing “normal” (i.e., not misfolded) a-syn. In people with Parkinson’s disease, the misfolded a-syn from their CSF causes the normal a-syn in the test tube to clump together. But in people who do not have Lewy bodies the normal a-syn in the test tube does not clump together.

This breakthrough is the result of many years of research to develop the a-syn-SAA. Once developed, the test was then used in thousands of CSF samples collected through the Parkinson’s Progression Markers Initiative (PPMI), funded by the Michael J. Fox Foundation.

What about DLB?

As of today, it is unknown whether the test will work as well in people with or at risk for DLB as it does in Parkinson’s disease. The a-syn-SAA is being studied in people with DLB, including through the LBDA Research Centers of Excellence, and preliminary results are promising for early diagnosis of DLB. But the existing data are not yet as extensive for DLB as for Parkinson’s disease. More research is needed to understand how well the test works in the various Lewy body disorders. This work is a high priority and LBDA is committed to quickly sharing updates with you about how the a-syn-SAA may apply to diagnosis of DLB in the future.

Should I get the test?

At this time, it is unknown how well the a-syn-SAA test will work in everyday clinical practice, so the test is not yet offered by most doctors. The LBDA and our scientific advisors are waiting for more data before making any recommendations on the use of the a-syn-SAA test outside of specialty clinics.

How can I help?

More research needs to be done, and people with Lewy body dementias and their family members can participate in research studies that will help scientists and physicians better understand how the test performs. If you are interested in learning more about research studies that might be right for you, consider signing up for Lewy Trial Tracker to be notified when new studies open up.


Siderowf A, Concha-Marambio L, Lafontant DE, et al., 2023. Assessment of heterogeneity among participants in the Parkinson’s Progression Markers Initiative cohort using α-synuclein seed amplification: a cross-sectional study. Lancet Neurology, 22(5):407-417. doi: 10.1016/S1474-4422(23)00109-6.