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ResearchSquare
Research Square
American Journal Experts

10.21203/rs.3.rs-4369598/v1
10.21203/rs.3.rs-4369598
preprint
1
Article
Analysis of alpha-synuclein harvested from intra-cranial instruments used in deep brain stimulation surgery for Parkinson’s disease
sorrentino zachary
Riklan Joshua
Lloyd Grace
Lucke-Wold Brandon
Mampre David
Quintin Stephan
Zakare-Fagbamila Rasheedat
Still Megan
Chandra Vyshak
Foote Kelly
Giasson Benoit
Hilliard Justin
20 5 2024
rs.3.rs-4369598https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
https://www.researchsquare.com/article/rs-4369598/v1
nihpp-rs4369598v1.pdf
Abstract

Alpha-synuclein (αSyn) forms pathologic aggregates in Parkinson’s disease (PD) and is implicated in mechanisms underlying neurodegeneration. While pathologic αSyn has been extensively studied, there is currently no method to evaluate αSyn within the brains of living patients. Patients with PD are often treated with deep brain stimulation (DBS) surgery in which surgical instruments are in direct contact with neuronal tissue; herein, we describe a method by which tissue is purified from DBS surgical instruments in PD and essential tremor (ET) patients and demonstrate that αSyn is robustly detected. 24 patients undergoing DBS surgery for PD (17 patients) or ET (7 patients) were enrolled; from patient samples, 81.2 ± 44.8 µg protein (n=15) is able to be purified, with immunoblot assays specific for αSyn reactive in all tested samples. Light microscopy revealed axons and capillaries as the primary components of purified tissue (n=3). Further analysis was conducted using western blot, demonstrating that truncated αSyn (1-125 αSyn) was significantly increased in PD (n=5) compared to ET (n=3), in which αSyn misfolding is not expected (0.64 ± 0.25 vs. 0.25 ± 0.12, P = 0.046), thus showing that pathologic αSyn can be reliably purified from living PD patients with this method.
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