Distinct serum anti-Aβ antibody patterns in hemorrhagic and inflammatory cerebral amyloid angiopathy manifestations

ObjectiveTo study blood anti-A{beta} antibodies in the context of spontaneous inflammatory or hemorrhagic CAA manifestations, which are similar to complications occurring after monoclonal anti-A{beta} antibody immunotherapies. MethodsIn this case-control study, serum anti-A{beta} antibody isotype, concentration, avidity, and reactivity toward soluble or fibrillary A{beta}1-40 and A{beta}1-42 isoforms were assessed using an ELISA-based multiplex analysis. Anti-A{beta} serologic patterns were defined in CAA and CAA subgroups using multivariable logistic regression analyses. ResultsFourty-one healthy aged controls and 64 CAA patients were recruited: 46 with hemorrhagic features (CAA-he) and 18 with CAA-related inflammation (CAA-ri). As compared to controls, the most striking features of CAA-related serological profiles were the following: i) both CAA-he and CAA-ri patients displayed lower binding diversity of anti-soluble A{beta}1-40 IgM; ii) CAA-he patients displayed higher anti-soluble A{beta}1-40 / fibrillary A{beta}1-42 IgG4 concentrations ratio and higher anti-soluble A{beta}1-42 IgG4 and IgA avidity; iii) CAA-ri patients displayed higher binding diversity of anti-soluble A{beta}1-40 IgG3 and higher anti-fibrillary/soluble A{beta}1-42 IgG4 dilution curve steepness ratio. ConclusionThis proof-of-concept study revealed anti-A{beta} antibody variations in CAA patients, some of which were associated to CAA clinical phenotypes, unveiling pathophysiological insights regarding CAA-hemorrhagic and inflammatory related events.