Objective: To examine the prevalence of phosphorylated alpha-synuclein in nerve fibers in patients with essential tremor (ET) and ET plus.

Background: Although Essential Tremor (ET) and Parkinson’s disease (PD) have been recognized as clinically distinct entities, parkinsonian features may be present in some patients with ET, categorized as “ET Plus”. Furthermore, prospective epidemiological studies have provided evidence that individuals with ET are 4-5 times more likely to develop PD.^1,2  A biomarker is needed that would reliably identify individuals with ET who are at higher risk of developing PD.  A novel method to detect phosphorylated alpha-synuclein deposits along nerves from skin biopsy samples, has been demonstrated to have high sensitivity and specificity in distinguishing patients with PD and other synucleinopathies from healthy controls.³ Thus, we sought to examine the prevalence of phosphorylated alpha-synuclein in skin biopsy samples of individuals with ET and ET plus.

Method: Individuals with ET or ET plus, as defined by the 2018 Movement Disorder Society (MDS) Consensus Statement,⁴ were prospectively recruited at Baylor College of Medicine in Houston, Texas. Patients were evaluated using The Essential Tremor Rating Assessment Scale (TETRAS), part III of the MDS-Unified Parkinson’s Disease Rating (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) and the University of Pennsylvania Smell Identification Test (UPSIT). DaTscan results were collected. Skin punch biopsies were performed at 3 sites using the Syn-One test. A positive test was defined as the presence of alpha-synuclein in at least one of the three samples.

Results: A total of 23 patients have been recruited, including 12 ET (mean age 68+/- 10.5 years, 9M/12) and 11 ET plus (mean age 71+/- 4.8 years, 7M/11) with positivity rates of 66.7% (8/12) for ET and 72.7% (8/11) for ET Plus. Although limited by small sample size, there were no significant differences in clinical scales or UPSIT scores between biopsy positive and negative patients. DaTscan was positive in 2 of 8 positive-biopsy patients.

Conclusion: We describe a surprisingly high prevalence of phosphorylated alpha-synuclein deposits in skin nerve fibers of patients with ET and ET Plus. Our findings suggest that this subset of ET patients may be at risk for developing PD or that the skin biopsy results reflect false positive findings.

References: 1. Tarakad A, Jankovic J. Essential Tremor and Parkinson’s Disease: Exploring the Relationship. Tremor Other Hyperfine Mov (N Y). 2019 Jan 9;8:589.

2. Louis ED, Berry D, Ghanem A, Cosentino SA. Conversion rate of essential tremor to essential tremor Parkinson disease: Data from a prospective longitudinal study. Neurol Clin Pract. 2023;13(3):e200162. doi:10.1212/CPJ.0000000000200162

3. Gibbons C, Levine T, Adler C, et al. Skin Biopsy Detection of Phosphorylated α-Synuclein in Patients with Synucleinopathy. JAMA. 2024 Mar 20. doi:10.1001/jama.2024.0792

4. Bhatia KP, Bain P, Bajaj N, et al. Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society. Mov Disord Off J Mov Disord Soc. 2018;33(1):75-87. doi:10.1002/mds.27121

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/prevalence-of-phosphorylated-alpha-synuclein-in-skin-biopsies-of-essential-tremor-patients/