We previously showed that a mutated form of apomyoglobin, i.e., W7FW14F, undergoes a nucleation-dependent polymerization reaction that results in the formation of amyloid fibrils identical to those formed by proteins involved in amyloid diseases . Although the W7FW14F apomyoglobin mutant is un25316-40-9 related to any human disease, it is a suitable model for amyloid aggregation studies because it forms amyloid-like fibrils under physiological conditions of pH and temperature. Under these experimental conditions, wild-type apomyoglobin is in the globular, a-helical native state. In the present study, we used W7FW14F apomyoglobin to study the effect of GAGs, mainly heparin and related compounds on the various kinetic phases of W7FW14F apomyoglobin amyloid aggregation. The results show that both the extent and rate of formation of amyloid fibrils are greatly enhanced by heparin and certain other GAGs, but not by the neutral and positively charged polymers dextran and polylysine. The amyloid aggregates formed in the presence of heparin appear to be harmless. Thus, heparin eliminates cytotoxic oligomeric species by promoting the formation of benign fibrils. Interestingly, we found that heparin induces early toxic aggregates also in wild-type apomyoglobin . This could open a debate regarding the therapeutic use of heparin. The effect of heparin as modulator of the amyloid aggregation of the W7FW14F apomyoglobin mutant was explored using absorbance, CD, FTIR, ThT fluorescence and EM measurements. We previously showed that, similar to the wild-type protein, the W7FW14F mutant is fully unfolded at pH 2.0 and partially folded at a pH near 4.0. When pH is increased from 4.0 to 7.0, the mutant protein aggregates and forms amyloid fibrils by a characteristic nucleation-dependent polymerization mechanism, whereas the wild-type protein folds correctly . At the beginning of the aggregation process, the aggregating protein molecules have a native-like conformation with an abundant alpha-helical content. These species assemble to form oligomeric species that, between 12 and 24 h, give rise to amyloid-like protofilaments. The latter develop slowly to form, after 5�C6 days, protofibrils that then associate further to form the higher order amyloid fibrils. The early aggregates have the structural characteristics of amyloid precursors, namely, the ability to bind ThT and Congo red, and an extensive Reversine b-sheet structure .