New Research Suggests Skin Test Can Detect Dementia with Lewy Bodies

May 29, 2024

Many people who have dementia with Lewy bodies (DLB) experience delay and difficulty with receiving an accurate diagnosis, often seeing multiple specialists before being correctly diagnosed. In general medical practice today, a diagnosis of DLB is made based on medical history and examination. This is sometimes accompanied by laboratory tests to support the diagnosis, such as special types of brain scans, measures of brain activity, imaging of the nerves supplying the heart, and sleep tests. However, these tests do not measure the protein most widely believed to be associated with Parkinson’s disease (PD) and DLB: misfolded alpha-synuclein. Definitive diagnoses have only been possible after death, when deposits of misfolded alpha-synuclein can be confirmed under a microscope.

In recent years, research has led to ways of measuring the protein alpha-synuclein in living people in by examining cerebrospinal fluid (CSF – which surrounds and supports the brain and spinal cord) or in small samples of tissues such as skin or saliva glands. In specialized research centers, scientists are studying whether such measures may help make more accurate diagnoses possible during life.

One way researchers are doing this is by is by examining nerve fibers in small skin samples. In the Syn-One Test, for example, three small pieces of skin are biopsied, one from the neck/shoulder area, one from the ankle, and one from the thigh. The samples are sent to a laboratory, where other researchers take a closer look at the nerve fibers coursing through the skin. These fibers are a “window” into the brain, and the presence in the skin biopsy of a specific form of alpha-synuclein called phosphorylated alpha-synuclein (or P-SYN) may be a telltale sign.

To test this, researchers funded by the NIH enlisted the participation of several hundred volunteers in a clinical trial called the Synuclein-One Study. The participants included 50 people with diagnosed with DLB and 96 people diagnosed with PD. The P-SYN test result was positive in 93% of participants with PD and 96% of participants with DLB. To ensure that the test was really measuring something related to the disease, though, the researchers also had to show that people without one of these diseases wouldn’t also have a positive P-SYN test. Among the volunteers, there were 120 participants without evidence of any disease associated with alpha-synuclein, and in this group, the P-SYN test came back negative 97% of the time. Taken together, these results suggest that skin tests may one day become an important and common part of the diagnostic process. In fact, they are already being used today in some clinical trials.

Research into this technique continues. The Syn-D Study is currently seeking volunteers with evidence of early stage DLB. If you are interested in learning more about the Syn-D Study, you can visit the Syn-D Study page on our website. LBDA encourages you to learn more about this and other currently recruiting clinical studies by visiting our clinical trials page. And if you would like to be alerted when new studies become available, please consider signing up for the Lewy Trial Tracker.

*For more information on this topic, see the recent LBDA Community Webinar Introduction to Synuclein Biomarkers: How Researchers are “Seeing” Lewy Bodies in the Living Brain.


McKeith IG, Boeve BF, Dickson DW, et al. 2017. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology, 89:88-100. DOI: 10.1212/WNL.0000000000004058

Gibbons CH, Levine T, Adler C, et al. 2024. Skin biopsy detection of phosphorylated α-synuclein in patients with synucleinopathies. Journal of the American Medical Association (JAMA). DOI: 10.1001/jama.2024.0792