Cook Sarah E V, Menšíková Kateřina, Koníčková Dorota, Šlanhofová Hedvika, Klíčová Kateřina, Raška Milan, Zapletalová Jana, Friedecký David, Kaňovský Petr
Department of Neurology, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic.
Department of Neurology, University Hospital Olomouc, Olomouc, Czech Republic.
J Neural Transm (Vienna). 2025 Mar 3. doi: 10.1007/s00702-025-02902-6.
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.
虽然大多数神经退行性疾病的诊断标准已经确立并得到验证，但各个疾病分类实体之间存在相当大的重叠，这仍然是一个重大的诊断挑战。越来越多的证据表明，神经退行性变通常由中枢神经系统内的炎症引发。炎症的识别可以作为病理生理过程的首个信号。因此，经过验证的神经炎症生物标志物（“生物标志物”）至关重要。本研究旨在评估三种神经退行性疾病中炎症生物标志物的存在情况和水平：路易体病（LBD）、多系统萎缩（MSA）和4重复tau蛋白病（4RT）。共纳入83例LBD患者、24例MSA患者和31例4RT患者，并与83名对照受试者进行比较。对脑脊液（CSF）和血清中的六种免疫相关蛋白进行了分析：C3补体、C4补体、触珠蛋白、转铁蛋白、类粘蛋白和β2微球蛋白（β2M）。协方差分析显示，与对照组相比，LBD（CSF：转铁蛋白、C3补体、类粘蛋白；血清：类粘蛋白、β2M）和MSA（CSF：转铁蛋白、C3补体、C4补体、类粘蛋白）中几种炎症生物标志物的水平显著降低。在C3补体的血清水平方面，突触核蛋白病患者组（LBD和MSA）与4RT之间也观察到显著差异。此外，与对照组相比，疾病组中LBD和MSA的转铁蛋白以及LBD的C3补体的脑脊液/血清商显著降低。这些发现表明，炎症过程可能在神经退行性蛋白病的病理生理中起作用，需要进一步研究来证实这些关联。识别潜在的体液生物标志物将是该领域有前景的进展。
