TY - JOUR
T1 - CSF SerpinA1 in Creutzfeldt–Jakob disease and frontotemporal lobar degeneration
AU - Abu-Rumeileh, Samir
AU - Halbgebauer, Steffen
AU - Steinacker, Petra
AU - Anderl-Straub, Sarah
AU - Polischi, Barbara
AU - Ludolph, Albert C.
AU - Capellari, Sabina
AU - Parchi, Piero
AU - Otto, Markus
N1 - Ricercatore distaccato presso IRCCS a seguito Convenzione esclusiva con Università di Bologna (Capellari Sabina, Parchi Piero)
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Objective: SerpinA1 (alpha-1 antitrypsin) is an acute inflammatory protein, which seems to play a role in neurodegeneration and neuroinflammation. In Alzheimer’s disease and synucleinopathies, SerpinA1 is overexpressed in the brain and the cerebrospinal fluid (CSF) showing abnormal patterns of its charge isoforms. To date, no comprehensive studies explored SerpinA1 CSF isoforms in Creutzfeldt–Jakob disease (CJD) and frontotemporal lobar degeneration (FTLD). Methods: Using a capillary isoelectric focusing immunoassay, we analyzed CSF SerpinA1 isoforms in control cases (n = 31) and patients with a definite or probable diagnosis of CJD (n=77) or FTLD (n = 30), belonging to several disease subtypes. Results: The overall SerpinA1 signal was significantly higher than in controls in CJD subtypes linked to abnormal prion protein (PrPSc) type 1, such as sporadic CJD (sCJD) MM(V)1, and in FTLD-TDP. Moreover, CJD linked to PrPSc type 1 and FTLD-TAU groups showed a significant relative increase of acidic and basic isoforms in comparison with controls, thereby forming two distinct SerpinA1 isoform profiles. Interpretation: CJD linked to PrPSc type 1 and FTLD show a differential upregulation and post-translational modifications of CSF SerpinA1. Further studies are needed to clarify whether these findings may reflect a common, albeit disease-specific, pathogenetic mechanism related to neurodegeneration.
AB - Objective: SerpinA1 (alpha-1 antitrypsin) is an acute inflammatory protein, which seems to play a role in neurodegeneration and neuroinflammation. In Alzheimer’s disease and synucleinopathies, SerpinA1 is overexpressed in the brain and the cerebrospinal fluid (CSF) showing abnormal patterns of its charge isoforms. To date, no comprehensive studies explored SerpinA1 CSF isoforms in Creutzfeldt–Jakob disease (CJD) and frontotemporal lobar degeneration (FTLD). Methods: Using a capillary isoelectric focusing immunoassay, we analyzed CSF SerpinA1 isoforms in control cases (n = 31) and patients with a definite or probable diagnosis of CJD (n=77) or FTLD (n = 30), belonging to several disease subtypes. Results: The overall SerpinA1 signal was significantly higher than in controls in CJD subtypes linked to abnormal prion protein (PrPSc) type 1, such as sporadic CJD (sCJD) MM(V)1, and in FTLD-TDP. Moreover, CJD linked to PrPSc type 1 and FTLD-TAU groups showed a significant relative increase of acidic and basic isoforms in comparison with controls, thereby forming two distinct SerpinA1 isoform profiles. Interpretation: CJD linked to PrPSc type 1 and FTLD show a differential upregulation and post-translational modifications of CSF SerpinA1. Further studies are needed to clarify whether these findings may reflect a common, albeit disease-specific, pathogenetic mechanism related to neurodegeneration.
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U2 - 10.1002/acn3.50980
DO - 10.1002/acn3.50980
M3 - Article
C2 - 31957347
AN - SCOPUS:85078669267
VL - 7
SP - 191
EP - 199
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
SN - 2328-9503
IS - 2
ER -