Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov;39(11):2087-2091.
doi: 10.1002/mds.29935. Epub 2024 Jul 18.

Skin α-Synuclein Seeding Activity in Patients with Type 1 Gaucher Disease

Mary Kate LoPiccolo  1 , Zerui Wang  2 , Gadi Maayan Eshed  3 , Luca Fierro  1 , Chanan Stauffer  1 , Kelly Wang  1 , Jing Zhang  4 , Curtis Tatsuoka  5 , Manisha Balwani  1 , Wen-Quan Zou  2   6 , Roy N Alcalay  3   7
Affiliations

Skin α-Synuclein Seeding Activity in Patients with Type 1 Gaucher Disease

Mary Kate LoPiccolo et al. Mov Disord. 2024 Nov.

Abstract

Background: Patients with type 1 Gaucher disease (GD1) have a significantly increased risk of developing Parkinson's disease (PD).

Objective: The objective of this study was to evaluate skin α-synuclein (αSyn) seeding activity as a biomarker for GD1-related PD (GD1-PD).

Methods: This single-center study administered motor and cognitive examinations and questionnaires of nonmotor symptoms to adult patients with GD1. Optional skin biopsy was performed for skin αSyn seed amplification assay (αSyn SAA) using real-time quaking-induced conversion assay.

Results: Forty-nine patients were enrolled, and 36 underwent skin biopsy. Two study participants had PD. Ten participants were αSyn SAA positive (27.8%), 7 (19.4%) were intermediate, and 19 (52.8%) were negative. Positive αSyn seeding activity was observed in the single GD1-PD case who consented to biopsy. αSyn SAA positivity was associated with older age (p = 0.043), although αSyn SAA positivity was more prevalent in patients with GD1 than historic controls.

Conclusions: Longitudinal follow-up is required to determine whether skin αSyn seeding activity can be an early biomarker for GD1-PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: Gaucher disease; Parkinson's disease; biomarkers; α‐synuclein seed amplification assay; α‐synuclein seeding activity.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest: The authors declare that there are no conflicts of interest relevant to this work.

References

    1. Hughes DA, Pastores GM. Gaucher Disease. In: Adam MP, Feldman J, Mirzaa GM, et al. , eds. GeneReviews®. University of Washington, Seattle; 1993. Accessed March 20, 2024. http://www.ncbi.nlm.nih.gov/books/NBK1269/ - PubMed
    1. Vanier MT, Caillaud C, Levade T. Disorders of Sphingolipid Synthesis, Sphingolipidoses, Niemann-Pick Disease Type C and Neuronal Ceroid Lipofuscinoses. In: Saudubray JM, Baumgartner MR, García-Cazorla Á, Walter J, eds. Inborn Metabolic Diseases. Springer; Berlin Heidelberg; 2022:735–764. doi: 10.1007/978-3-662-63123-2_40 - DOI
    1. Sidransky E, Nalls MA, Aasly JO, et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease. N Engl J Med. 2009;361(17):1651–1661. doi: 10.1056/NEJMoa0901281 - DOI - PMC - PubMed
    1. Balwani M, Mistry PK, Di Fonzo AB, et al. Age-specific risk of Parkinson’s disease and Parkinsonian syndrome in patients with Gaucher disease type 1: Real-world evidence from the International Collaborative Gaucher Group Gaucher Registry. Mol Genet Metab. 2024;141(2):107767. doi: 10.1016/j.ymgme.2023.107767 - DOI
    1. Rosenbloom B, Balwani M, Bronstein JM, et al. The incidence of Parkinsonism in patients with type 1 Gaucher disease: data from the ICGG Gaucher Registry. Blood Cells Mol Dis. 2011;46(1):95–102. doi: 10.1016/j.bcmd.2010.10.006 - DOI - PMC - PubMed