Title | Anti-amyloid β autoantibodies in cerebral amyloid angiopathy-related inflammation: implications for amyloid-modifying therapies. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Piazza, F, Greenberg, SM, Savoiardo, M, Gardinetti, M, Chiapparini, L, Raicher, I, Nitrini, R, Sakaguchi, H, Brioschi, M, Billo, G, Colombo, A, Lanzani, F, Piscosquito, G, Carriero, MRita, Giaccone, G, Tagliavini, F, Ferrarese, C, DiFrancesco, JC |
Journal | Ann Neurol |
Volume | 73 |
Issue | 4 |
Pagination | 449-58 |
Date Published | 2013 Apr |
ISSN | 1531-8249 |
Keywords | Adult, Aged, Amyloid beta-Peptides, Apolipoproteins E, Autoantibodies, Brain, Case-Control Studies, Cerebral Amyloid Angiopathy, Female, Humans, Inflammation, Male, Middle Aged, Peptide Fragments, Phosphorylation, Retrospective Studies, Steroids, tau Proteins |
Abstract | 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. |
DOI | 10.1002/ana.23857 |
Alternate Journal | Ann. Neurol. |
PubMed ID | 23625526 |