While diagnostic criteria have been established and validated for most neurodegenerative diseases, the considerable overlap between individual nosological entities remains a significant diagnostic challenge. Increasing evidence suggests that neurodegeneration is often initiated by inflammation within the central nervous system. The identification of inflammation could serve as a first signal of the pathophysiological process. As such, validated biological markers ("biomarkers") of neuroinflammation are critically important. This study aimed to assess the presence and levels of inflammatory biomarkers in three neurodegenerative diseases: Lewy body diseases (LBD), multiple system atrophy (MSA), and 4-repeat tauopathies (4RT). A total of 83 LBD, 24 MSA, and 31 4RT patients were included, with 83 control subjects for comparison. Six immune-related proteins were analysed in cerebrospinal fluid (CSF) and blood serum (serum): C3 complement, C4 complement, haptoglobin, transferrin, orosomucoid, and β2 microglobulin (β2M). ANCOVA statistical analysis revealed significantly lower levels of several inflammatory biomarkers in LBD (CSF: transferrin, C3 complement, orosomucoid; Serum: orosomucoid, β2M) and MSA (CSF: transferrin, C3 complement, C4 complement, orosomucoid) compared to controls. Significant differences were also observed between the synucleinopathy patient groups (LBD and MSA) and 4RT in serum levels of C3 complement. Additionally, the CSF/serum quotients for transferrin (LBD and MSA) and C3 complement (LBD) were significantly lower in disease relative to controls. These findings suggest that inflammatory processes may play a role in the pathophysiology of neurodegenerative proteinopathies, warranting further research to confirm these associations. The identification of potential fluid biomarkers would then represent a promising step forward in the field.

• Keywords
• 4-repeat tauopathies, Alpha-synucleinopathies, Biomarkers, Neurodegenerative diseases, Neuroinflammation, Parkinsonism,
• MeSH
• Biomarkers blood   cerebrospinal fluid   MeSH
• Lewy Body Disease * blood   cerebrospinal fluid   MeSH
• Middle Aged MeSH
• Humans MeSH
• Multiple System Atrophy * blood   cerebrospinal fluid   MeSH
• Neuroinflammatory Diseases * blood   cerebrospinal fluid   MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Tauopathies * blood   cerebrospinal fluid   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Biomarkers MeSH

Neuroactive steroids are a group of steroid molecules that are involved in the regulation of functions of the nervous system. The nervous system is not only the site of their action, but their biosynthesis can also occur there. Neuroactive steroid levels depend not only on the physiological state of an individual (person's sex, age, diurnal variation, etc.), but they are also affected by various pathological processes in the nervous system (some neurological and psychiatric diseases or injuries), and new knowledge can be gained by monitoring these processes. The aim of our research was to develop and validate a comprehensive method for the simultaneous determination of selected steroids with neuroactive effects in human serum. The developed method enables high throughput and a sensitive quantitative analysis of nine neuroactive steroid substances (pregnenolone, progesterone, 5α-dihydroprogesterone, allopregnanolone, testosterone, 5α-dihydrotestosterone, androstenedione, dehydroepiandrosterone, and epiandrosterone) in 150 μL of human serum by ultrahigh-performance liquid chromatography with tandem mass spectrometry. The correlation coefficients above 0.999 indicated that the developed analytical procedure was linear in the range of 0.90 nmol/L to 28.46 μmol/L in human serum. The accuracy and precision of the method for all analytes ranged from 83 to 118% and from 0.9 to 14.1%, respectively. This described method could contribute to a deeper understanding of the pathophysiology of various diseases. Similarly, it can also be helpful in the search for new biomarkers and diagnostic options or therapeutic approaches.

• Keywords
• neuroactive steroids, neurosteroids, serum, ultrahigh-performance liquid chromatography−tandem mass spectrometry,
• MeSH
• Humans MeSH
• Neurosteroids blood   MeSH
• Reproducibility of Results MeSH
• Steroids blood   analysis   MeSH
• Tandem Mass Spectrometry * methods   MeSH
• Chromatography, High Pressure Liquid methods   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH