Abstract

We report the changed levels of serum amyloid alpha, an immunologically active protein, in Parkinson’s disease (PD) patients’ peripheral tissues. We have previously shown that Saa-1 and -2 (serum amyloid alpha-1,-2, genes) were among the top downregulated genes in PD patients’ skin, using whole-genome RNA sequencing. In the current study, we characterized the gene and protein expression profiles of skin and blood samples from patients with confirmed PD diagnosis and age/sex matched controls. qRT-PCR analysis of PD skin demonstrated downregulation of Saa-1 and -2 genes in PD patients. However, the lowered amount of protein could not be visualized using immunohistochemistry, due to low quantity of SAA (Serum Amyloid Alpha, protein) in skin. Saa-1 and -2 expression levels in whole blood were below detection threshold based on RNA sequencing, however significantly lowered protein levels of SAA1/2 in PD patients’ serum were shown with ELISA, implying that SAA is secreted into the blood. These results show that SAA is differentially expressed in the peripheral tissues of PD patients.

Highlights

  • Parkinson’s disease (PD) is a neurodegenerative disorder, characterized by motor symptoms, like resting tremor, hypo- and bradykinesia, rigidity and postural instability (Poewe et al, 2017)

  • Our previous work with skin RNA-sequencing showed a significant downregulation of Saa-1 and -2 expression levels in PD patients

  • The immunohistochemical analysis of 13 PD patients’ and 12 controls’ skins for expression of Serum amyloid alpha (SAA) 1/2 protein, demonstrated that no visually detectable protein or changes in protein levels can be observed in PD patients (Figure 2)

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Summary

Introduction

Parkinson’s disease (PD) is a neurodegenerative disorder, characterized by motor symptoms, like resting tremor, hypo- and bradykinesia, rigidity and postural instability (Poewe et al, 2017). Pathogenic biomolecular defects of PD occur in non-neuronal peripheral tissues (Braak et al, 2003; Auburger et al, 2012; Teves et al, 2018). As to date the affirmative diagnosis of PD can only be made based on the results of post-mortem autopsy, there is a great need for detailed understanding of disease biology, as SAA in Peripheral Tissues of PD well as for studies investigating novel diagnostic and prognostic biomarkers. Peripheral blood has been widely used in the search for biomarkers in PD (Scherzer et al, 2007; Grünblatt et al, 2010; Borrageiro et al, 2017), other peripheral tissues, such as skin, are promising models for investigating the pathogenic mechanisms of PD

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