Complement activation by the amyloid proteins A beta peptide and beta 2-microglobulin.

Area of Science:

• Immunology
• Neuroscience
• Biochemistry

Background:

• Complement activation (CA) is implicated in Alzheimer's disease (AD) pathogenesis.
• Investigating the role of CA in general amyloidogenesis is crucial.
• Amyloid fibril proteins are potential activators of the complement system.

Purpose of the Study:

• To assess the complement activation potential of various amyloid fibril proteins.
• To determine if amyloidogenesis is influenced by complement activation.
• To compare the CA capabilities of different amyloid proteins and their forms.

Main Methods:

• Solid-phase system (ELISA) and liquid-phase system (complement consumption assay) were employed.
• Tested complement activation by A beta preparations (soluble, protofilaments, fibrils).
• Evaluated complement activation by beta 2-microglobulin (beta 2M) and Amyloid A-protein.

Main Results:

• Fibrillar A beta induced modest CA with slow kinetics; soluble A beta showed no CA in liquid phase.
• Fibrillar A beta induced CA at concentrations of 200 mg/ml and higher.
• Soluble beta 2M from dialysates was a potent CA, similar to A beta; urine-derived beta 2M was less active.
• A beta and beta 2M activated complement via the classical pathway.
• Amyloid-associated molecules did not significantly alter A beta-induced CA.

Conclusions:

• Both fibrillar A beta and beta 2M oligomers can induce complement activation.
• Beta 2M from dialysis-associated amyloidosis patients showed significant CA potential.
• Complement activation by these amyloid proteins occurs at supra-physiological concentrations.