Anti-amyloid β autoantibodies in cerebral amyloid angiopathy-related inflammation: implications for amyloid-modifying therapies

Ann Neurol. 2013 Apr;73(4):449-58. doi: 10.1002/ana.23857. Epub 2013 Apr 26.


Objective: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is characterized by vasogenic edema and multiple cortical/subcortical microbleeds, sharing several aspects with the recently defined amyloid-related imaging abnormalities (ARIA) reported in Alzheimer's disease (AD) passive immunization therapies. Herein, we investigated the role of anti-amyloid β (Aβ) autoantibodies in the acute and remission phases of CAA-ri.

Methods: We used a novel ultrasensitive technique on patients from a retrospective multicenter case-control study, and evaluated the anti-Aβ autoantibody concentration in the cerebrospinal fluid (CSF) of 10 CAA-ri, 8 CAA, 14 multiple sclerosis, and 25 control subjects. Levels of soluble Aβ40, Aβ42, tau, P-181 tau, and APOE genotype were also investigated.

Results: During the acute phase of CAA-ri, anti-Aβ autoantibodies were specifically increased and directly correlated with Aβ mobilization, together with augmented tau and P-181 tau. Following clinical and radiological remission, autoantibodies progressively returned to control levels, and both soluble Aβ and axonal degeneration markers decreased in parallel.

Interpretation: Our data support the hypothesis that the pathogenesis of CAA-ri may be mediated by a selective autoimmune reaction against cerebrovascular Aβ, directly related to autoantibody concentration and soluble Aβ. The CSF dosage of anti-Aβ autoantibodies with the technique here described can thus be proposed as a valid alternative tool for the diagnosis of CAA-ri. Moreover, given the similarities between ARIA developing spontaneously and those observed during immunization trials, anti-Aβ autoantibodies can be considered as novel potential biomarkers in future amyloid-modifying therapies for the treatment of AD and CAA.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Amyloid beta-Peptides / immunology
  • Apolipoproteins E / genetics
  • Autoantibodies / cerebrospinal fluid*
  • Brain / pathology
  • Case-Control Studies
  • Cerebral Amyloid Angiopathy* / cerebrospinal fluid
  • Cerebral Amyloid Angiopathy* / complications
  • Cerebral Amyloid Angiopathy* / immunology
  • Female
  • Humans
  • Inflammation* / cerebrospinal fluid
  • Inflammation* / etiology
  • Inflammation* / immunology
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid
  • Phosphorylation
  • Retrospective Studies
  • Steroids / therapeutic use
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Autoantibodies
  • Peptide Fragments
  • Steroids
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • tau Proteins