International Journal of Molecular Sciences (Jun 2022)

Specific Cerebrospinal Fluid SerpinA1 Isoform Pattern in Alzheimer’s Disease

  • Lorenzo Barba,
  • Steffen Halbgebauer,
  • Federico Paolini Paoletti,
  • Giovanni Bellomo,
  • Samir Abu-Rumeileh,
  • Petra Steinacker,
  • Federico Massa,
  • Lucilla Parnetti,
  • Markus Otto

DOI
https://doi.org/10.3390/ijms23136922
Journal volume & issue
Vol. 23, no. 13
p. 6922

Abstract

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SerpinA1 (α1-antitrypsin) is a soluble glycoprotein, the cerebrospinal fluid (CSF) isoforms of which showed disease-specific changes in neurodegenerative disorders that are still unexplored in Alz-heimer’s disease (AD). By means of capillary isoelectric focusing immunoassay, we investigated six serpinA1 isoforms in CSF samples of controls (n = 29), AD-MCI (n = 29), AD-dem (n = 26) and Lewy body disease (LBD, n = 59) patients and correlated the findings with CSF AD core biomarkers (Aβ42/40 ratio, p-tau, t-tau). Four CSF serpinA1 isoforms were differently expressed in AD patients compared to controls and LBD patients, especially isoforms 2 and 4. AD-specific changes were found since the MCI stage and significantly correlated with decreased Aβ42/40 (p p < 0.001). Analysis of serpinA1 isoform provided good di-agnostic accuracy in discriminating AD patients versus controls (AUC = 0.80) and versus LBD patients (AUC = 0.92), with best results in patients in the dementia stage (AUC = 0.97). SerpinA1 isoform expression is altered in AD patients, suggesting a common, albeit disease-specific, in-volvement of serpinA1 in most neurodegenerative disorders.

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