Immune complexes of auto-antibodies against Aβ1-42 peptides patrol cerebrospinal fluid of non-Alzheimer's patients
The diagnostic potential of large A β -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. Mole...
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Veröffentlicht in: | Molecular psychiatry 2007-06, Vol.12 (6), p.601-610 |
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Sprache: | eng |
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Zusammenfassung: | The diagnostic potential of large A
β
-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 (A
β
1-42). 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-A
β
and anti-IgG antibodies confirmed that LAP-4 type consisted of A
β
and IgG aggregates. Our results assign a central role to the immune system in regulating A
β
1-42 homeostasis by clustering this peptide in immunocomplexes. |
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ISSN: | 1359-4184 1476-5578 |
DOI: | 10.1038/sj.mp.4001947 |