Immune complexes of auto-antibodies against Aβ1-42 peptides patrol cerebrospinal fluid of non-Alzheimer's patients

Abstract

The diagnostic potential of large Aβ-peptide binding particles (LAPs) in the cerebrospinal fluid (CSF) of Alzheimer's dementia (AD) patients and non-AD controls (nAD) was evaluated. LAPs were detected by confocal spectroscopy in both groups with high inter-individual variation in number. Molecular imaging by confocal microscopy revealed that LAPs are heterogeneous superaggregates that could be subdivided morphologically into four main types (LAP1-4). LAP-4 type, resembling a 'large chain of pearls', was detected in 42.1% of all nAD controls but it was virtually absent in AD patients. LAP-4 type could be selectively removed by protein A beads, a clear indication that it contained immunoglobulins in addition to beta-amyloid peptides (Aβ1-42). We observed a close correlation between LAPs and immunoglobulin G (IgG) concentration in CSF in controls but not in AD patients. Double labeling of LAPs with anti-Aβ and anti-IgG antibodies confirmed that LAP-4 type consisted of Aβ and IgG aggregates. Our results assign a central role to the immune system in regulating Aβ1-42 homeostasis by clustering this peptide in immunocomplexes. © 2007 Nature Publishing Group All rights reserved.