title: Aggregation state-dependent activation of the classical complement pathway by the amyloid beta peptide.
abstract: Activation of the classical complement pathway has been widely investigated in recent years as a potential mechanism for the neuronal loss and neuritic dystrophy characteristic of Alzheimer's disease (AD) pathogenesis. We have previously shown that amyloid beta peptide (A beta) is a potent activator of complement, and recent evidence suggesting that the assembly state of A beta is crucial to the progress of the disease prompted efforts to determine whether the ability of A beta to activate the classical complement pathway is a function of the aggregation state of the peptide. In this report, we show that the fibrillar aggregation state of A beta, as determined by thioflavin T fluorometry, electron microscopy, and staining with Congo red and thioflavine S, is precisely correlated with the ability of the peptide to induce the formation of activated fragments of the complement proteins C4 and C3. These results suggest that the classical complement pathway provides a mechanism whereby complement-dependent processes may contribute to neuronal injury in the proximity of fibrillar but not diffuse A beta deposits in the AD brain.
authors.affiliation: L.J. Roberts Center for Alzheimer's Research, Sun Health Research Institute, Sun City, Arizona 85372, U.S.A.
authors.forename: S
authors.initials: S
authors.lastname: Webster
authors.forename: B
authors.initials: B
authors.lastname: Bradt
authors.forename: J
authors.initials: J
authors.lastname: Rogers
authors.forename: N
authors.initials: N
authors.lastname: Cooper
mesh_terms: D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000378:metabolism / Q000494:pharmacology*; D052160:Benzothiazoles; D004396:Coloring Agents; D003167:Complement Activation / Q000187:drug effects*; D003224:Congo Red; D005456:Fluorescent Dyes; D006801:Humans; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000032:analysis* / Q000378:metabolism / Q000494:pharmacology*; D013844:Thiazoles
chemical_list: D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D004396:Coloring Agents; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C009462:thioflavin T; D003224:Congo Red