Premium
Aggregation State‐Dependent Activation of the Classical Complement Pathway by the Amyloid β Peptide
Author(s) -
Webster Scott,
Bradt Bonnie,
Rogers Joseph,
Cooper Neil
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69010388.x
Subject(s) - thioflavin , complement system , peptide , classical complement pathway , alternative complement pathway , amyloid (mycology) , senile plaques , p3 peptide , activator (genetics) , amyloid beta , chemistry , beta (programming language) , microbiology and biotechnology , biophysics , biochemistry , biology , neuroscience , alzheimer's disease , amyloid precursor protein , immunology , antibody , disease , medicine , pathology , receptor , computer science , inorganic chemistry , programming language
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 β peptide (Aβ) is a potent activator of complement, and recent evidence suggesting that the assembly state of Aβ is crucial to the progress of the disease prompted efforts to determine whether the ability of Aβ 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 Aβ, 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 Aβ deposits in the AD brain.