Objective: This study aims to evaluate the causal relationship between plasma alpha-internexin levels and the risk of Parkinson’s disease (PD).

Background: Alpha-internexin, implicated in neuronal development and axonal outgrowth, is a neuronal-specific intermediate filament protein widely expressed in the central nervous system. Previous studies have suggested that overexpression of alpha-internexin is related to motor coordination deficits and involved in several neurodegenerative diseases. However, whether alpha-internexin levels are causally associated with PD is largely unknown.

Method: We conducted a two-sample Mendelian randomization (MR) study to evaluate the causal relationship between alpha-internexin levels and the risk of PD. The summary-level data for plasma alpha-internexin levels (id: “prot-a-1551”) and PD (id: “ieu-b-2”) used in this MR study were retrieved from the OpenGWAS using the TwosampleMR package (version 0.5.7) in R software (version 4.3.2) [1]. There were seven instrumental variables available for alpha-internexin levels (P<5E-06). Five different statistical methods were used to calculate the MR estimates. Pleiotropy and heterogeneity analyses were performed to confirm the robustness of the findings.

Results: The MR estimate using the inverse variance weighted (IVW) method showed that plasma alpha-internexin levels were causally linked to a higher risk of PD (OR=1.22, 95%CI=1.05-1.43, P= 0.009). Sensitivity analysis using other approaches showed similar results with the same trend (Figure 1). No obvious horizontal pleiotropy or heterogeneity was found in the MR-Egger test or Cochran’s Q test, indicating good reliability.

Conclusion: The present MR study demonstrates that higher plasma alpha-internexin levels are causally associated with an increased risk of PD, which might serve as a potential biomarker for PD.

Figure 1

References: 1. Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, Laurin C, Burgess S, Bowden J, Langdon R: The MR-Base platform supports systematic causal inference across the human phenome. elife 2018, 7:e34408.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/increased-alpha-internexin-levels-are-associated-with-a-higher-risk-of-parkinsons-disease/