Objective: The aim of this study was to determine whether cerebrospinal fluid (CSF) levels of transferrin differ between patients with Parkinson´s disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and healthy controls (HC) or in general between the groups of α-synucleinopathies and tauopathies.

Background: Transferrin is one of the key proteins involved in iron homeostasis within the CNS. Iron is an essential trace element for the numerous biological processes in neurons and glial cells. Its deficiency leads to cell death, on the contrary it is cytotoxic when there is an excess. Impaired iron homeostasis can induce toxic protein oligomers and abnormal intracellular aggregates; the aggregation of a-synuclein and tau protein has been shown in vitro to be triggered by iron.

Method: CSF transferrin levels were compared between groups of patients suffering from PD (n=77), MSA (n=24), PSP (n=24), CBD (n=7) and HC (n=90) and subsequently between the groups of α-synucleinopathies (n=101) and tauopathies (n=31). Mann-Whitney U test and Spearman correlation analysis were used for statistical analysis; tests were performed at a significance level of 0.05.

Results: A significantly lower CSF transferrin level (p=0.012) was present in the PD group when compared to HC. Significantly higher CSF level of transferrin was found in the group of tauopathies when compared to α-synucleinopathies (p=0.024).

Conclusion: The specific role of iron in the development of neurodegenerative proteinopathies has not been elucidated yet. Transferrin cannot enter the brain from the blood directly, and the iron transport in the brain is mediated by transferrin synthesized by oligodendrocytes and choroid plexus epithelial cells. CSF transferrin levels, which varies depending mutually on the amount of iron in the brain, may reflect differences between underlying pathophysiology of neurodegenerative proteinopathies; transferrin therefore might be one of the CSF biomarkers useful for their differential diagnosis.

Supported by: the European Regional Development Fund – Project ENOCH (No. Z.02.1.01/0.0/0.0/16_019/0000868) and IGA-LF-2023-015.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/transferrin-as-a-possible-csf-biomarker-in-neurodegenerative-proteinopathies/